MedWorm: Molecular Biology

P21 and p27: roles in carcinogenesis and drug resistance

Expert Reviews in Molecular Medicine — Fri, 04 Jul 2008 11:09:25 +0100

Review ArticlesAbde M. Abukhdeir, Ben Ho Park, Expert Reviews in Molecular Medicine, Volume 10 , pp e19AbstractHuman cancers arise from an imbalance of cell growth and cell death. Key proteins that govern this balance are those that mediate the cell cycle. Several different molecular effectors have been identified that tightly regulate specific phases of the cell cycle, including cyclins, cyclin-dependent kinases (CDKs) and CDK inhibitors. Notably, loss of expression or function of two G1-checkpoint CDK inhibitors has been implicated in the genesis or progression of many human malignancies. Additionally, there is a growing body of evidence suggesting that functional loss of p21 or p27 can mediate a drug-resistance phenotype. However, reports in the literature have also suggested p21 and p27 can promote tumours, indicating a paradoxical effect. Here, we review historic and recent studies of these two CDK inhibitors, including their identification, function, importance to carcinogenesis and finally their roles in drug resistance. (Source: Expert Reviews in Molecular Medicine)

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Therapeutic immunomodulators from nematode parasites

Expert Reviews in Molecular Medicine — Fri, 04 Jul 2008 11:09:25 +0100

Review ArticlesWilliam Harnett, Margaret M. Harnett, Expert Reviews in Molecular Medicine, Volume 10 , pp e18AbstractThere has been an alarming increase in the incidence of autoimmune and allergic diseases in Western countries in the past few decades. However, in countries endemic for parasitic helminth infections, such diseases remain relatively rare. Hence, it has been hypothesised that helminths may protect against the development of autoimmunity and allergy. This article reviews the evidence supporting this idea with respect to helminths of the phylum Nematoda (nematodes), considering data from human studies and animal models of inflammatory disease. The nature and mode of action of nematode-derived molecules with immunomodulatory properties are considered, and their therapeutic efficacy in models of autoimmunity and allergy described. The recent and future use of nematodes and their products in treating human disease are also discussed. (Source: Expert Reviews in Molecular Medicine)

Galectins: structure, function and therapeutic potential

Expert Reviews in Molecular Medicine — Fri, 04 Jul 2008 11:09:25 +0100

Review ArticlesRi-Yao Yang, Gabriel A. Rabinovich, Fu-Tong Liu, Expert Reviews in Molecular Medicine, Volume 10 , pp e17AbstractGalectins are a family of animal lectins that bind protein interactions with other cytoplasmic and nuclear proteins. Current research indicates that galectins play important roles in diverse physiological and pathological processes, including immune and inflammatory responses, tumour development and progression, neural degeneration, atherosclerosis, diabetes, and wound repair. Some of these have been discovered or confirmed by using genetically engineered mice deficient in a particular galectin. Thus, galectins may be a therapeutic target or employed as therapeutic agents for inflammatory diseases, cancers and several other diseases. (Source: Expert Reviews in Molecular Medicine)

Advances in mouse models of prostate cancer

Expert Reviews in Molecular Medicine — Fri, 04 Jul 2008 11:09:25 +0100

Review ArticlesImran Ahmad, Owen J. Sansom, Hing Y. Leung, Expert Reviews in Molecular Medicine, Volume 10 , pp e16AbstractAdvances in science and technology have allowed us to manipulate the mouse genome and analyse the effect of specific genetic alterations on the development of prostate cancer in vivo. We can now analyse the molecular basis of initiation, invasion and progression to metastatic disease. The current mouse models utilise knockout, knock-in or conditional regulation of expression using Cre hits PTENloxP/loxP mouse is the only model that spans the entire continuum from initiation to local invasion and metastasis. Such mouse models increase our understanding of the disease process and provide targets for novel therapeutic approaches. Hopefully, the transgenic models will become inducible and ultimately allow both temporal and spatial gene inactivation. Compound mutational models will also develop further, with double and triple knock-in or knockout systems adding to our knowledge of the interaction between different signalling cascades. (Source: Expert Reviews in Molecular Medicine)

Research highlights

Nature Structural and Molecular Biology — Fri, 04 Jul 2008 07:28:04 +0100

Research highlights Nature Structural & Molecular Biology 15, 699 (2008). doi:10.1038/nsmb0708-699 (Source: Nature Structural and Molecular Biology)

Bringing it together

Nature Structural and Molecular Biology — Fri, 04 Jul 2008 07:28:04 +0100

Bringing it together Nature Structural & Molecular Biology 15, 653 (2008). doi:10.1038/nsmb0708-653 An in-depth look at membrane fusion—a process essential for communication within and between cells—is presented in this issue of Nature Structural & Molecular Biology. (Source: Nature Structural and Molecular Biology)

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Some classic papers in the field of membrane fusion—a personal view

Nature Structural and Molecular Biology — Fri, 04 Jul 2008 07:28:04 +0100

Some classic papers in the field of membrane fusion—a personal view Nature Structural & Molecular Biology 15, 655 (2008). doi:10.1038/nsmb0708-655 Author: Reinhard Jahn Every field of research has influential papers that have shaped and guided future work. Reinhard Jahn gives his picks for membrane fusion and a little bit of history about how the field has developed. (Source: Nature Structural and Molecular Biology)

Acute neonatal glucocorticoid exposure produces selective and rapid cerebellar neural progenitor cell apoptotic death

Cell Death and Differentiation — Fri, 04 Jul 2008 04:00:00 +0100

Acute neonatal glucocorticoid exposure produces selective and rapid cerebellar neural progenitor cell apoptotic death Cell Death and Differentiation advance online publication, July 4, 2008. doi:10.1038/cdd.2008.97 Authors: K K Noguchi, K C Walls, D F Wozniak, J W Olney, K A Roth & N B Farber (Source: Cell Death and Differentiation)

On the role of major vault protein in the resistance of senescent human diploid fibroblasts to apoptosis

Cell Death and Differentiation — Fri, 04 Jul 2008 04:00:00 +0100

On the role of major vault protein in the resistance of senescent human diploid fibroblasts to apoptosis Cell Death and Differentiation advance online publication, July 4, 2008. doi:10.1038/cdd.2008.96 Authors: S J Ryu, H J An, Y S Oh, H R Choi, M K Ha & S C Park (Source: Cell Death and Differentiation)

Does autophagy have a license to kill mammalian cells?

Cell Death and Differentiation — Fri, 04 Jul 2008 04:00:00 +0100

Does autophagy have a license to kill mammalian cells? Cell Death and Differentiation advance online publication, July 4, 2008. doi:10.1038/cdd.2008.101 Authors: F Scarlatti, R Granata, A J Meijer & P Codogno (Source: Cell Death and Differentiation)

Transcriptomic analysis of saccharomyces cerevisiae physiology in the context of galactose assimilation perturbations

RSC - Mol. BioSyst. latest articles — Fri, 04 Jul 2008 04:00:00 +0100

C. Syriopoulos, A. Panayotarou, K. Lai, Maria I. Klapa (Paper from Mol. BioSyst.) C. Syriopoulos, Mol. BioSyst., 2008, DOI: 10.1039/b718732g To cite this article before page numbers are assigned, use the DOI form of citation above. The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Mol. BioSyst. latest articles)

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Small molecule enhancers of autophagy for neurodegenerative diseases

RSC - Mol. BioSyst. latest articles — Fri, 04 Jul 2008 04:00:00 +0100

Sovan Sarkar, David C. Rubinsztein (Highlight from Mol. BioSyst.) Sovan Sarkar, Mol. BioSyst., 2008, DOI: 10.1039/b804606a To cite this article before page numbers are assigned, use the DOI form of citation above. The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Mol. BioSyst. latest articles)

Biosensor recognition elements.

Current Issues in Molecular Biology — Thu, 03 Jul 2008 13:43:38 +0100

Biosensor recognition elements.

Curr Issues Mol Biol. 2008;10(1-2):1-12

Authors: Chambers JP, Arulanandam BP, Matta LL, Weis A, Valdes JJ

PMID: 18525101 [PubMed - in process]

(Source: Current Issues in Molecular Biology)

Considerations in the development of live biotherapeutic products for clinical use.

Current Issues in Molecular Biology — Thu, 03 Jul 2008 13:43:38 +0100

Considerations in the development of live biotherapeutic products for clinical use.

Curr Issues Mol Biol. 2008;10(1-2):13-6

Authors: Ross JJ, Boucher PE, Bhattacharyya SP, Kopecko DJ, Sutkowski EM, Rohan PJ, Chandler DK, Vaillancourt J

Food products in the United States (U.S.), including dietary supplements, may contain live microorganisms and can be promoted for general health, nutritional, or structure/function claims. In contrast, such preparations used with the intention of having a preventive or therapeutic effect in humans are regulated by the Food and Drug Administration (FDA) in the U.S. as biological products, specifically as live biotherapeutic products (LBPs). Discussion of considerations in the early development of LBPs may aid in preparation of an Investigational New Drug Application (IND) that is designed to collect clinical data to support marketing approval of a LBP in the U.S. for a specific clinical use. Product information is an important component of an IND to support a proposed clinical study.

PMID: 18525102 [PubMed - in process]

(Source: Current Issues in Molecular Biology)

Long-term stability of the human gut microbiota in two different rat strains.

Current Issues in Molecular Biology — Thu, 03 Jul 2008 13:43:38 +0100

Long-term stability of the human gut microbiota in two different rat strains.

Curr Issues Mol Biol. 2008;10(1-2):17-24

Authors: Alpert C, Sczesny S, Gruhl B, Blaut M

Human microbiota associated rats are frequently used as a model to study host microbe interactions. This study investigated the long-term stability of the bacterial community in such rats. Following the association of two strains of germ-free rats (12 male animals each) with fecal bacteria from a human donor the development of the microbiota was monitored for 12 months by PCR-denaturing gradient gel electrophoresis. During this time the Dice similarity coefficient (Cs) for the fecal microbial community of the rats associated with a human microbiota in comparison to the donor sample ranged between 73% +/- 8 and 74% +/- 3 for the Wistar and the Fischer 344 rats, respectively. After 12 months the similarity coefficients were 78% +/- 9 and 76% +/- 7, respectively, while the similarity coefficients for rat sample replicates ranged from 77% +/- 7 to 88% +/- 5; the similarity coefficient of the donor sample replicates was 78% +/- 9. DNA sequences of bands observed in the different denaturing gradient gel electrophoresis profiles exhibited the highest degree of identity to uncultured bacteria previously found in samples of human, mouse or pig intestinal origin. The results of this study suggest that the dominant human fecal microbiota can be maintained in the human microbiota associated rat model for at least one year.

PMID: 18525103 [PubMed - in process]

(Source: Current Issues in Molecular Biology)

Gene-environment interactions and epigenetic basis of human diseases.

Current Issues in Molecular Biology — Thu, 03 Jul 2008 13:43:38 +0100

Gene-environment interactions and epigenetic basis of human diseases.

Curr Issues Mol Biol. 2008;10(1-2):25-36

Authors: Liu L, Li Y, Tollefsbol TO

Most human diseases are related in some way to the loss or gain in gene functions. Regulation of gene expression is a complex process. In addition to genetic mechanisms, epigenetic causes are gaining new perspectives in human diseases related to gene deregulation. Most eukaryotic genes are packed into chromatin structures, which lead to high condensations of the genes that require dynamic chromatin remodeling processes to facilitate their transcription. DNA methylation and histone modifications represent two of the major chromatin remodeling processes. They also serve to integrate environmental signals for the cells to modulate the functional output of their genome. Complex human diseases such as cancer and type 2 diabetes are believed to have a strong environmental component in addition to genetic causes. Aberrancies in chromatin remodeling are associated with both genetically and environmentally-related diseases. We will focus on recent findings of the epigenetic basis of human metabolic disorders to facilitate further exploration of epigenetic mechanisms and better understandings of the molecular cues underlying such complex diseases.

PMID: 18525104 [PubMed - in process]

(Source: Current Issues in Molecular Biology)

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Immunomodulatory effects of probiotics in the intestinal tract.

Current Issues in Molecular Biology — Thu, 03 Jul 2008 13:43:38 +0100

Immunomodulatory effects of probiotics in the intestinal tract.

Curr Issues Mol Biol. 2008;10(1-2):37-54

Authors: Delcenserie V, Martel D, Lamoureux M, Amiot J, Boutin Y, Roy D

The intestinal microbiota is the largest source of microbial stimulation that exerts both harmful and beneficial effects on human health. The interaction between probiotic and enterocytes is the initiating event in immunomodulation and merits particular attention. The effects of probiotic is strain dependent and for each new probiotic strain, profiles of cytokines secreted by lymphocytes, enterocytes or dendritic cells that come in contact with the strain should be systematically established. To evaluate the effects of probiotics on the immune system, models that mimic the mucosa, and thus the physiological reality, should be preferred whenever it is possible. Then, the in vitro observed effects should be backed up by properly conducted randomized double bind clinical studies. More detailed studies are needed to determine the precise action mode of probiotics on both mucosal and systemic immunity.

PMID: 18525105 [PubMed - in process]

(Source: Current Issues in Molecular Biology)

Gene amplification from cryopreserved arabidopsis thaliana shoot tips.

Current Issues in Molecular Biology — Thu, 03 Jul 2008 13:43:38 +0100

Gene amplification from cryopreserved Arabidopsis thaliana shoot tips.

Curr Issues Mol Biol. 2008;10(1-2):55-60

Authors: Basu C

Cryopreservation is a way to store elite quality plant germplasms. The exact mechanism of stress tolerance during cryopreservation is unknown. Unavavailability of a detailed protocol for understanding the molecular genetics of plant cryostress is a major obstacle in plant cryobiology research. This paper describes the methods of extraction of total RNA from cryogenically stored plant tissues accompanied by successful amplication of cDNAs by reverse transcriptase PCR. The whole process can be completed in two to three days. Through this protocol, several genes were identified which were differentially expressed during cryostress. This protocol will help researchers to pursue further research in the field of molecular genetics of plant cryostress. Interesting genes identified via these processes can be cloned and plants can be transformed for the purpose of trait enhancement and modification.

PMID: 18525106 [PubMed - in process]

(Source: Current Issues in Molecular Biology)

The eph receptor/ephrin system: an emerging player in the invasion game.

Current Issues in Molecular Biology — Thu, 03 Jul 2008 13:43:38 +0100

The Eph receptor/ephrin system: an emerging player in the invasion game.

Curr Issues Mol Biol. 2008;10(1-2):61-6

Authors: Campbell TN, Robbins SM

Eph receptor tyrosine kinases (Ephs) and their membrane-anchored ligands (ephrins) form a vital cell communication system capable of bi-directional signaling. This Eph receptor/ephrin system has classically been demonstrated to play a role in development. However, emerging evidence has revealed differential expression of Ephs and ephrins in numerous cancers. Recent studies suggest that this system influences invasive behaviour, promoting a more aggressive and metastatic phenotype. Hence, this minireview summarizes the current understanding of the contribution of both Eph receptors and their ephrin ligands to invasiveness in cancer, as well as their use as potential therapeutic targets.

PMID: 18525107 [PubMed - in process]

(Source: Current Issues in Molecular Biology)

Growth factor effects on costal chondrocytes for tissue engineering fibrocartilage

Cell and Tissue Research — Thu, 03 Jul 2008 08:17:58 +0100

Abstract Tissue-engineered fibrocartilage could become a feasible option for replacing tissues such as the knee meniscus or temporomandibular joint disc. This study employed five growth factors (insulin-like growth factor-I, transforming growth factor-β1, epidermal growth factor, platelet-derived growth factor-BB, and basic fibroblast growth factor) in a scaffoldless approach with costal chondrocytes, attempting to improve biochemical and mechanical properties of engineered constructs. Samples were quantitatively assessed for total collagen, glycosaminoglycans, collagen type I, collagen type II, cells, compressive properties, and tensile properties at two time points. Most treated constructs had lower biomechanical and biochemical properties than the controls with no growth factors, suggesting a detrimental effect, but the treatment with insulin-like growth factor-I tended to improve the constructs. Additionally, the 6-week time point was consistently better than that at 3 weeks, with total collagen, glycosaminoglycans, and aggregate modulus doubling during this time. Further optimization of the time in culture and exogenous stimuli will be important in making a more functional replacement tissue. Content Type Journal ArticleCategory Regular ArticleDOI 10.1007/s00441-008-0652-2Authors D. E. Johns, Rice University Department of Bioengineering: MS-142 P.O. Box 1892 Houston TX 77251 USAK. A. Athanasiou, Rice University Department of Bioengineering: MS-142 P.O. Box 1892 Houston TX 77251 USA Journal Cell and Tissue ResearchOnline ISSN 1432-0878Print ISSN 0302-766X (Source: Cell and Tissue Research)

Protective effects of epigallocatechin gallate on colon preneoplastic lesion induced by 2-amino-3-methylimidazo [4, 5-f] quinoline in mice.

Molecular Medicine — Thu, 03 Jul 2008 04:00:00 +0100

Protective effects of Epigallocatechin gallate on colon preneoplastic lesion induced by 2-amino-3-methylimidazo [4, 5-f] quinoline in mice.

Mol Med. 2008 Jul 3;

Authors: Yuan JH, Li YQ, Yang XY

Epigallocatechin gallate (EGCG), a key active ingredient in green tea, has multiple anti-carcinogenic effects. The aim of the present study was to investigate if EGCG could prevent the formation of colon aberrant crypt foci (ACF) induced by 2-amino-3-methylimidazo [4, 5-f] quinoline (IQ) and to explore possible mechanisms for resultant effects. Sixty male BALB/cA nude, immunodeficient mice were divided into six groups including a normal unexposed control, mice induced with IQ alone, three groups treated with varying doses of EGCG post IQ induction and a EGCG-treated control population. Six weeks later, the mice were sacrificed and tissues were subjected to hematoxylin-eosin (HE) staining and 0.2% methylene blue staining to observe histopathological alterations of colon mucus and the formation of ACF, respectively. Protein expression of NF-E2-related factor 2 (Nrf2) was assessed via immunohistochemistry (IHC) and Western analysis and mRNA levels of Nrf2 and uridine 5'-diphosphate-glucuronosyltransferase (UGT)1A10 were determined in colon tissues. Our results demonstrate that, compared with IQ-induced controls, the degrees of atypical hyperplasia decreased and the number of total ACF and total AC also decreased significantly (P<0.05 and P<0.01, respectively) in mice belonging to all EGCG dosing groups. At the same time, the protein levels of Nrf2 detected by IHC and western blotting increased (both P<0.01, compared with IQ group), and the mRNA levels of Nrf2 and UGT1A10 increased evidently (both P<0.01, compared with IQ group). In conclusion, EGCG had preventive effects on preneoplastic lesion induced by IQ. Ourobservations suggest that this effect may be the result of activation of the Nrf2-UGT1A10 signaling pathway.

PMID: 18596869 [PubMed - as supplied by publisher]

(Source: Molecular Medicine)

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Identification of marker genes for differential diagnosis of chronic fatigue syndrome.

Molecular Medicine — Thu, 03 Jul 2008 04:00:00 +0100

Identification of Marker Genes for Differential Diagnosis of Chronic Fatigue Syndrome.

Mol Med. 2008 Jul 3;

Authors: Saiki T, Kawai T, Morita K, Ohta M, Saito T, Rokutan K, Ban N

Chronic fatigue syndrome (CFS) is a clinically defined condition characterized by long-lasting disabling fatigue. Because of the unknown mechanism underlying this syndrome, there is still no specific biomarker for objective assessment of the pathological fatigue. We have compared gene expression profiles in peripheral blood between 11 drug-free patients with CFS and age- and sex-matched healthy subjects using a custom microarray carrying complementary DNA probes for 1,467 stress-responsive genes. We identified 12 genes whose mRNA levels were significantly changed in CFS patients. Of these 12 genes, quantitative real-time PCR validated the changes in 9 genes encoding granzyme in activated T or natural killer cells (GZMA), energy regulators (ATP5J2, COX5B, and DBI), proteasome subunits (PSMA3 and PSMA4), putative protein kinase c inhibitor (HINT), GTPase (ARHC), and signal transducers and activators of transcription 5A (STAT5A). Next, we performed the same microarray analysis on 3 additional CFS patients and 20 other patients with the chief complaint of long-lasting fatigue related to other disorders (non-CFS patients) and found that the relative mRNA expression of 9 genes classified 79% (11/14) of CFS and 85% (17/20) of the non-CFS patients. Finally, real-time PCR measurements of the levels of the 9 involved mRNAs were done in another group of 18 CFS and 12 non-CFS patients. The expression pattern correctly classified 94% (17/18) of CFS and 92% (11/12) of non-CFS patients. Our results suggest that the defined gene cluster (9 genes) may be useful for detecting of pathological responses in CFS patients and for differential diagnosis of this syndrome.

PMID: 18596870 [PubMed - as supplied by publisher]

(Source: Molecular Medicine)

Membrane fusion

Nature Structural and Molecular Biology — Thu, 03 Jul 2008 04:00:00 +0100

Membrane fusion Nature Structural & Molecular Biology 15, 658 (2008). doi:10.1038/nsmb.1451 Authors: William Wickner & Randy Schekman (Source: Nature Structural and Molecular Biology)

Synaptic vesicle fusion

Nature Structural and Molecular Biology — Thu, 03 Jul 2008 04:00:00 +0100

Synaptic vesicle fusion Nature Structural & Molecular Biology 15, 665 (2008). doi:10.1038/nsmb.1450 Authors: Josep Rizo & Christian Rosenmund (Source: Nature Structural and Molecular Biology)

The fusion pores of ca2+-triggered exocytosis

Nature Structural and Molecular Biology — Thu, 03 Jul 2008 04:00:00 +0100

The fusion pores of Ca2+-triggered exocytosis Nature Structural & Molecular Biology 15, 684 (2008). doi:10.1038/nsmb.1449 Authors: Meyer B Jackson & Edwin R Chapman (Source: Nature Structural and Molecular Biology)

Viral membrane fusion

Nature Structural and Molecular Biology — Thu, 03 Jul 2008 04:00:00 +0100

Viral membrane fusion Nature Structural & Molecular Biology 15, 690 (2008). doi:10.1038/nsmb.1456 Author: Stephen C Harrison (Source: Nature Structural and Molecular Biology)

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Mechanics of membrane fusion

Nature Structural and Molecular Biology — Thu, 03 Jul 2008 04:00:00 +0100

Mechanics of membrane fusion Nature Structural & Molecular Biology 15, 675 (2008). doi:10.1038/nsmb.1455 Authors: Leonid V Chernomordik & Michael M Kozlov (Source: Nature Structural and Molecular Biology)

The palladium-catalysed copper-free sonogashira coupling of isoindoline nitroxides: a convenient route to robust profluorescent carbon-carbon frameworks

RSC - Organic Biomolecular Chemistry — Thu, 03 Jul 2008 04:00:00 +0100

Daniel J. Keddie, Kathryn E. Fairfull-Smith, Steven E. Bottle (Paper from Org. Biomol. Chem.) Daniel J. Keddie, Org. Biomol. Chem., 2008, DOI: 10.1039/b806963h To cite this article before page numbers are assigned, use the DOI form of citation above. The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

Polar [3 + 2] cycloaddition of ketones with electrophilically activated carbonyl ylides. synthesis of spirocyclic dioxolane indolinones

RSC - Organic Biomolecular Chemistry — Thu, 03 Jul 2008 04:00:00 +0100

Ghenia Bentabed-Ababsa, Aicha Derdour, Thierry Roisnel, Jose A. Saez, Luis R. Domingo, Florence Mongin (Paper from Org. Biomol. Chem.) Ghenia Bentabed-Ababsa, Org. Biomol. Chem., 2008, DOI: 10.1039/b804856h To cite this article before page numbers are assigned, use the DOI form of citation above. The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

Generation of molecular diversity using a complexity-generating mcr-platform towards triazinane diones

RSC - Organic Biomolecular Chemistry — Thu, 03 Jul 2008 04:00:00 +0100

Bas Groenendaal, Eelco Ruijter, Frans J. J. de Kanter, Martin Lutz, Anthony L. Spek, Romano V. A. Orru (Paper from Org. Biomol. Chem.) Bas Groenendaal, Org. Biomol. Chem., 2008, DOI: 10.1039/b807138a To cite this article before page numbers are assigned, use the DOI form of citation above. The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

Analysis of systemic sulfur metabolism in plants using integrated '-omics' strategies

RSC - Mol. BioSyst. latest articles — Thu, 03 Jul 2008 04:00:00 +0100

Masami Yokota Hirai, Kazuki Saito (Highlight from Mol. BioSyst.) Masami Yokota Hirai, Mol. BioSyst., 2008, DOI: 10.1039/b802911n To cite this article before page numbers are assigned, use the DOI form of citation above. The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Mol. BioSyst. latest articles)

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Involvement of jnk regulation in oxidative stress-mediated murine liver injury by microcystin-lr

Apoptosis — Wed, 02 Jul 2008 15:34:40 +0100

Abstract Microcystin-LR (MC-LR) produced by cyanobacteria in diverse water systems is a potent specific hepatotoxin and has been documented to induce various liver diseases via oxidative stress. However, the underlying mechanisms are largely unknown. In the current study, we investigated the molecular events involved in the oxidative liver injury by MC-LR. Our results demonstrated that MC-LR induced liver injury in mice through a series of steps that began with the production of reactive oxygen species (ROS), which stimulated the sustained activation of JNK and its downstream targets, AP-1 and Bid. Furthermore, the mitochondrial proteomic analysis indicated that JNK activation affected some crucial enzymes of energy metabolism, led to mitochondria dysfunction, which contributed to hepatocyte apoptosis and oxidative liver injury by MC-LR. Our results reveal significant insights into the mechanisms of liver injury induced by microcystins, and serve as a framework for deciphering the role of JNK in oxidative stress-associated liver diseases. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s10495-008-0237-2Authors Yinna Wei, Nanjing University State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science Nanjing 210093 People’s Republic of ChinaDan Weng, Nanjing University State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science Nanjing 210093 People’s Republic of ChinaFeng Li, Nanjing University State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science Nanjing 210093 People’s Republic of ChinaXiao Zou, Peking University Proteome Group, National Laboratory of Protein Engineering and Plant Genetic Engineering, College of Life Sciences Beijing People’s Republic of ChinaD. Owen Young, Nanjing University State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science Nanjing 210093 People’s Republic of ChinaJianguo Ji, Peking University Proteome Group, National Laboratory of Protein Engineering and Plant Genetic Engineering, College of Life Sciences Beijing People’s Republic of ChinaPingping Shen, Nanjing University State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science Nanjing 210093 People’s Republic of China Journal ApoptosisOnline ISSN 1573-675XPrint ISSN 1360-8185 (Source: Apoptosis)

Erratum

Nature Cell Biology — Wed, 02 Jul 2008 06:43:09 +0100

Erratum Nature Cell Biology 10, 874 (2008). doi:10.1038/ncb0708-874 (Source: Nature Cell Biology)

Research highlights

Nature Cell Biology — Wed, 02 Jul 2008 06:43:09 +0100

Research highlights Nature Cell Biology 10, 764 (2008). doi:10.1038/ncb0708-764 (Source: Nature Cell Biology)

Signalling links

Nature Cell Biology — Wed, 02 Jul 2008 06:43:09 +0100

Signalling links Nature Cell Biology 10, 753 (2008). doi:10.1038/ncb0708-753b Our papers now link directly to relevant Molecule Page database entries at the Signaling Gateway (Source: Nature Cell Biology)

Birthday precedings

Nature Cell Biology — Wed, 02 Jul 2008 06:43:09 +0100

Birthday precedings Nature Cell Biology 10, 753 (2008). doi:10.1038/ncb0708-753a As some of the new 'web 2.0'-enabled publishing ventures mature, we take stock of their utility to the community (Source: Nature Cell Biology)

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Opposing roles for glypicans in hedgehog signalling

Nature Cell Biology — Wed, 02 Jul 2008 06:43:09 +0100

Opposing roles for glypicans in Hedgehog signalling Nature Cell Biology 10, 761 (2008). doi:10.1038/ncb0708-761 Authors: Dong Yan & Xinhua Lin Glypican members of the heparan sulphate proteoglycan family regulate several developmental signalling pathways, such as those involving Hedgehog, Wnt, BMP and FGF. Two studies reveal opposite effects of glypicans on Hedgehog signalling and show how their core protein domains and GPI anchor contribute to their versatile biological functions. (Source: Nature Cell Biology)

Cdh1: a master g0/g1 regulator

Nature Cell Biology — Wed, 02 Jul 2008 06:43:09 +0100

Cdh1: a master G0/G1 regulator Nature Cell Biology 10, 755 (2008). doi:10.1038/ncb0708-755 Authors: Jeffrey R. Skaar & Michele Pagano APC/CCdh1 controls the G0 and G1 phases of the cell cycle. Using a conditional knockout of the Cdh1 coding gene Fizzy-related (Fzr), a new study demonstrates that Cdh1 is essential for viability and that it functions as a tumour suppressor by preventing genomic instability. (Source: Nature Cell Biology)

Uvrag reveals its second nature

Nature Cell Biology — Wed, 02 Jul 2008 06:43:09 +0100

UVRAG reveals its second nature Nature Cell Biology 10, 759 (2008). doi:10.1038/ncb0708-759 Authors: Karolina Peplowska, Margarita Cabrera & Christian Ungermann UVRAG, a known regulator of autophagosome formation, also promotes autophagosome maturation by recruiting the fusion machinery of the late endosome. (Source: Nature Cell Biology)

Breaking down emt

Nature Cell Biology — Wed, 02 Jul 2008 06:43:09 +0100

Breaking down EMT Nature Cell Biology 10, 757 (2008). doi:10.1038/ncb0708-757 Authors: Romain Levayer & Thomas Lecuit Epithelial–mesenchymal transition, in which epithelial cells lose their polarity and become motile mesenchymal cells, occurs during development and marks a key step in tumour progression towards metastasis. Most studies of this process have focused on the disassembly of adherens junctions, but regulation of basement membrane breakdown by a pathway involving RhoA and microtubules may be equally important. (Source: Nature Cell Biology)

Large-scale quantitative lc-ms/ms analysis of detergent-resistant membrane proteins from rat renal collecting duct.

Am J Physiol Cell Ph... — Wed, 02 Jul 2008 04:00:00 +0100

Large-scale quantitative LC-MS/MS analysis of detergent-resistant membrane proteins from rat renal collecting duct.

Am J Physiol Cell Physiol. 2008 Jul 2;

Authors: Yu MJ, Pisitkun T, Wang G, Aranda JF, Gonzales PA, Tchapyjnikov D, Shen RF, Alonso MA, Knepper MA

In the renal collecting duct, vasopressin controls transport of water and solutes via regulation of membrane transporters such as aquaporin-2 (AQP2) and the epithelial urea transporter, UT-A. To discover proteins potentially involved in vasopressin action in rat kidney collecting ducts, membrane "raft" proteins were enriched by harvesting detergent-resistant membranes (DRMs) of the inner medullary collecting duct (IMCD) cells. Proteins were identified and quantified with LC-MS/MS. A total of 814 proteins were identified in the DRM fractions. Of these, 186 were enriched in the DRMs including several characteristic raft proteins. Immunoblotting confirmed DRM enrichment of representative proteins. Immunofluorescence confocal microscopy of rat IMCDs with antibodies to DRM proteins demonstrated heterogeneity of raft subdomains: MAL2 (apical region), RalA (predominant basolateral labeling), caveolin-2 (punctate labeling distributed throughout the cells), and flotillin-1 (discrete labeling of large intracellular structures). The DRM proteome included GPI-anchored, doubly acylated, singly acylated, chlolesterol-binding, and integral membrane proteins (IMPs). The IMPs were on average much smaller and more hydrophobic than IMPs identified in IMCD without DRM enrichment. The content of serine 256-phosphorylated AQP2 was greater in DRM than in non-DRM fractions. Vasopressin did not change the DRM-to-non-DRM ratio of most proteins, whether quantified by LC-MS/MS (n=22) or immunoblotting (n=6). However, Rab7 and annexin-2 showed small increases in the DRM fraction in response to vasopressin. In accord with the long-term goal of creating a systems level analysis of transport regulation, this study has identified a large number of membrane-associated proteins expressed in the IMCD that have potential roles in vasopressin action. Key words: vasopressin, Aquaporin-2, membrane raft, mass spectrometry.

PMID: 18596208 [PubMed - as supplied by publisher]

(Source: Am J Physiol Cell Ph...)

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Connective tissue growth factor inhibits adipocyte differentiation.

Am J Physiol Cell Ph... — Wed, 02 Jul 2008 04:00:00 +0100

Connective tissue growth factor inhibits adipocyte differentiation.

Am J Physiol Cell Physiol. 2008 Jul 2;

Authors: Tan JT, McLennan SV, Song WW, Lo LW, Bonner JG, Williams PF, Twigg SM

Adipocyte differentiation is a key process implicated in the pathogenesis of obesity and insulin resistance. Its regulation is triggered by a cascade of transcription factors, including the CCAAT/enhancer binding proteins (C/EBPs) and PPARgamma. Growth factors such as transforming growth factor-beta1 (TGF-beta1) are known to inhibit adipocyte differentiation in vitro via the C/EBP pathway, and in vivo, but whether a downstream mediator of TGF-beta1, connective tissue growth factor (CTGF) also known as CCN2, has a similar role, is unknown. Mouse 3T3-L1 cells were differentiated into adipocytes using standard methods and effects and regulation of CTGF were studied. Intervention with rhCTGF during differing stages of differentiation caused an inhibition in the development of the adipocyte phenotype, according to the gene expression of the differentiation markers adiponectin and PPARgamma, as well as suppression of lipid accumulation and expression of the lipogenic enzyme, glycerol-3-phophate dehydrogenase. While CTGF gene expression promptly fell by 90% as 3T3-L1 preadipocytes differentiated into mature adipocytes, CTGF mRNA expression was induced by added TGF-beta1. CTGF applied to cells early in the course of differentiation inhibited total cell protein levels and nuclear localization of the beta isoform of C/EBP (C/EBP-beta) and subsequently, total cell C/EBP-alpha levels. CTGF also inhibited the adipocyte differentiation program in primary cultures of mouse predipocytes. Expression of CTGF mRNA was two-fold higher in the central fat depots of mice compared with subcutaneous fat, suggesting a potential role for CTGF in vivo. In summary, these data show that CTGF inhibits the adipocyte differentiation program. Key words: ccn2; connective tissue growth factor, adipocyte differentiation, NIH3t3.

PMID: 18596209 [PubMed - as supplied by publisher]

(Source: Am J Physiol Cell Ph...)

Actin cytoskeletal dynamics in smooth muscle: a new paradigm for the regulation of smooth muscle contraction.

Am J Physiol Cell Ph... — Wed, 02 Jul 2008 04:00:00 +0100

Actin Cytoskeletal Dynamics in Smooth Muscle: A New Paradigm for the Regulation of Smooth Muscle Contraction.

Am J Physiol Cell Physiol. 2008 Jul 2;

Authors: Gunst SJ, Zhang W

A growing body of data supports a view of the actin cytoskeleton of smooth muscle cells as a dynamic structure that plays an integral role in regulating the development of mechanical tension and the material properties of smooth muscle tissues. The increase in the proportion of filamentous actin that occurs in response to the stimulation of smooth muscle cells and the essential role of stimulus-induced actin polymerization and cytoskeletal dynamics in the generation of mechanical tension has been convincingly documented in many smooth muscle tissues and cells using a wide variety of experimental approaches. Most of the evidence suggests that the functional role of actin polymerization during contraction is distinct and separately regulated from the actomyosin crossbridge cycling process. The molecular basis for the regulation of actin polymerization and its physiologic roles may vary in diverse types of smooth muscle cells and tissues. However, current evidence supports a model for smooth muscle contraction in which contractile stimulation initiates the assembly of cytoskeletal/extracellular matrix adhesion complex proteins at the membrane, and proteins within this complex orchestrate the polymerization and organization of a submembraneous network of actin filaments. This cytoskeletal network may serve to strengthen the membrane for the transmission of force generated by the contractile apparatus to the extracellular matrix, and to enable the adaptation of smooth muscle cells to mechanical stresses. Better understanding of the physiologic function of these dynamic cytoskeletal processes in smooth muscle may provide important insights into the physiological regulation of smooth muscle tissues. Key words: actin polymerization, smooth muscle tissue, adhesion junction, contractile activation, cytoskeletal signaling.

PMID: 18596210 [PubMed - as supplied by publisher]

(Source: Am J Physiol Cell Ph...)

P2x7 receptor-pannexin1 complex: pharmacology and signaling.

Am J Physiol Cell Ph... — Wed, 02 Jul 2008 04:00:00 +0100

P2X7 receptor-Pannexin1 complex: Pharmacology and signaling.

Am J Physiol Cell Physiol. 2008 Jul 2;

Authors: Iglesias R, Locovei S, Roque AP, Alberto AP, Dahl G, Spray DC, Scemes E

Pannexin1 (Panx1), an ortholog to invertebrate innexin gap junctions, has recently been proposed to be the pore induced by P2X7 receptor activation. We explored the pharmacological action of compounds known to block gap junctions on Panx1 channels activated by the P2X7R and the mechanisms involved in the interaction between these two proteins. Whole cell recordings revealed distinct P2X7R and Panx1 currents in response to agonists. Activation of Panx1 currents following P2X7R stimulation or by membrane depolarization was blocked by Panx1 siRNA as well as with mefloquine > carbenoxolone > flufenamic acid. Incubation of cells with KN-62, a P2X7R antagonist, prevented current activation by BzATP. Membrane permeabilization to dye induced by BzATP was also prevented by Panx1 siRNA and by carbenoxolone and mefloquine. Membrane permeant (TAT-P2X7) peptides, provided evidence that the SH3-death domain of the C-terminus of the P2X7R is involved in the initial steps of the signal transduction events leading to Panx1 activation and that a Src tyrosine kinase is likely involved in this process. Competition assays indicated that 20 microM TAT-P2X7 peptide caused 50% reduction in Src binding to the P2X7R complex. Src tyrosine phosphorylation following BzATP stimulation was reduced by KN-62, TAT-P2X7 peptide and by the Src tyrosine inhibitor PP2, and that these compounds prevented both large conductance Panx1 currents and membrane permeabilization. These results together with the lack Panx1 tyrosine phosphorylation in response to P2X7R stimulation indicate the involvement of an additional molecule in the tyrosine kinase signal transduction pathway mediating Panx1 activation through the P2X7 receptor. Key words: gap junction blockers, permeabilization, P2Z, tyrosine kinase, src.

PMID: 18596211 [PubMed - as supplied by publisher]

(Source: Am J Physiol Cell Ph...)

Probenecid, a gout remedy, inhibits pannexin 1 channels.

Am J Physiol Cell Ph... — Wed, 02 Jul 2008 04:00:00 +0100

PROBENECID, A GOUT REMEDY, INHIBITS PANNEXIN 1 CHANNELS.

Am J Physiol Cell Physiol. 2008 Jul 2;

Authors: Silverman W, Locovei S, Dahl GP

Probenecid is a well-established drug for the treatment of gout and is thought to act on an organic anion transporter, thereby affecting uric acid excretion in the kidney by blocking urate reuptake. Probenecid has also been shown to affect ATP release, leading to the suggestion that ATP release involves an organic anion transporter. Other pharmacological evidence and the observation of dye uptake, however, suggest that the non-vesicular release of ATP is mediated by large membrane channels with pannexin 1 being a prominent candidate. Here we show that probenecid inhibits currents mediated by pannexin 1 channels in the same concentration range as observed for inhibition of transport processes. Probenecid did not affect channels formed by connexins. Thus, probenecid allows for discrimination between channels formed by connexins and pannexins. Key words: probenecid, pannexin, connexin, transport, ATP release.

PMID: 18596212 [PubMed - as supplied by publisher]

(Source: Am J Physiol Cell Ph...)

Cytoskeletal remodeling in differentiated vascular smooth muscle is actin isoform-dependent and stimulus-dependent.

Am J Physiol Cell Ph... — Wed, 02 Jul 2008 04:00:00 +0100

Cytoskeletal Remodeling in Differentiated Vascular Smooth Muscle is Actin Isoform-Dependent and Stimulus-Dependent.

Am J Physiol Cell Physiol. 2008 Jul 2;

Authors: Kim HR, Gallant C, Leavis PC, Gunst SJ, Morgan KG

Dynamic remodeling of the actin cytoskeleton plays an essential role in the migration and proliferation of vascular smooth muscle cells. It has been suggested that actin remodeling may also play an important functional role in non-migrating, non-proliferating differentiated vascular smooth muscle (dVSM). In the present study we show that contractile agonists increase the net polymerization of actin in dVSM, as measured by differential ultracentrifugation of vascular smooth muscle tissue and co-staining of single freshly dissociated cells with fluorescent probes specific for G and F actin. Furthermore, induced alterations of the actin polymerization state, as well as actin decoy peptides, inhibit contractility in a stimulus-dependent manner. Latrunculin pretreatment or actin decoy peptides significantly inhibit contractility induced by a phorbol ester or an alpha agonist, but these procedures have no effect on contractions induced by KCl. Aorta dVSM expresses alpha smooth muscle actin, beta actin, nonmuscle gamma actin and smooth muscle gamma actin. Incorporation of isoform-specific cell-permeant synthetic actin decoy peptides, as well as isoform-specific probing of cell fractions and 2-D gels, demonstrate that actin remodeling during alpha agonist contractions involves remodeling of primarily gamma actin and, to a lesser extent, beta actin. Taken together, these results show that net isoform-dependent and agonist-dependent increases in actin polymerization regulate vascular contractility. Key words: cytoskeletal remodeling, actin isoform, vascular smooth muscle, decoy peptide.

PMID: 18596213 [PubMed - as supplied by publisher]

(Source: Am J Physiol Cell Ph...)

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Ca2+ handling is altered when arterial myocytes progress from a contractile to a proliferative phenotype in culture.

Am J Physiol Cell Ph... — Wed, 02 Jul 2008 04:00:00 +0100

Ca2+ handling is altered when arterial myocytes progress from a contractile to a proliferative phenotype in culture.

Am J Physiol Cell Physiol. 2008 Jul 2;

Authors: Berra-Romani R, Mazzocco-Spezzia A, Pulina MV, Golovina VA

Phenotypic modulation of vascular myocytes is important for vascular development and adaptation. A characteristic feature of this process is alteration in intracellular Ca(2+) handling, which is not completely understood. Here, we studied mechanisms involved in functional changes of IP3- and ryanodine (RY)-sensitive Ca(2+) stores, store-operated Ca(2+) entry (SOCE) and receptor-operated Ca(2+) entry (ROCE) associated with arterial myocyte modulation from a contractile to a proliferative phenotype in culture. Proliferating, cultured myocytes from rat mesenteric artery have elevated resting cytosolic Ca(2+) levels and increased IP3-sensitive Ca(2+) store content. ATP- and cyclopiazonic acid (CPA, SERCA inhibitor)-induced Ca(2+) transients in Ca(2+)-free medium are significantly larger in proliferating arterial smooth muscle cells (ASMCs) than in freshly dissociated myocytes, whereas caffeine (CAF)-induced Ca(2+) release is much smaller. Moreover, the CAF/RY-sensitive store gradually loses sensitivity to CAF activation during cell culture. These changes can be explained by increased expression of all three IP3 receptors and a switch from RY receptor type II to type III expression during proliferation. SOCE, activated by depletion of the IP3/CPA-sensitive store, is greatly increased in proliferating ASMCs. Augmented SOCE and ROCE (activated by the diacylglycerol analog 1-oleoyl-2-acetyl-sn-glycerol) in proliferating myocytes can be attributed to upregulated expression of, respectively, transient receptor potential proteins, TRPC 1/4/5 and TRPC 3/6. Moreover, STIM1 and Orai proteins are upregulated in proliferating cells. Increased expression of IP3 receptors, SERCA2b, TRPCs, Orai(s) and STIM1 in proliferating ASMCs suggests that these proteins play a critical role in an altered Ca(2+) handling that occurs during vascular growth and remodeling. Key words: Store-operated Ca2+ entry, receptor-operated Ca2+ entry, TRPC proteins, STIM1.

PMID: 18596214 [PubMed - as supplied by publisher]

(Source: Am J Physiol Cell Ph...)

Febrile temperature leads to significant stiffening of plasmodium falciparum parasitized erythrocytes.

Am J Physiol Cell Ph... — Wed, 02 Jul 2008 04:00:00 +0100

Febrile temperature leads to significant stiffening of Plasmodium falciparum parasitized erythrocytes.

Am J Physiol Cell Physiol. 2008 Jul 2;

Authors: Marinkovic M, Diez-Silva M, Pantic I, Fredberg JJ, Suresh S, Butler JP

Parasitic infection with Plasmodium falciparum is responsible for the most severe form of human malaria, in which patients suffer from periodic fever. It is well established that during intraerythrocytic maturation of the parasite in the red blood cell (RBC), the RBC becomes significantly more cytoadhesive and less deformable; these and other biochemical factors together with human host factors such as compromised immune status are important contributors to the disease pathology. There is currently substantial interest in understanding the loss of RBC deformability due to P. falciparum infection, but few results are available concerning effects of febrile conditions or parasitization on RBC membrane rheology. Here, for the first time, we report rheology of the single, isolated RBC with and without P. falciparum merozoite invasion, spanning a range from room temperature to febrile conditions (41 degrees C), over all the stages of parasite maturation. As expected, stiffness increased with parasite maturation. Surprisingly, however, stiffness increased acutely with temperature on a scale of minutes, particularly in late trophozoite and schizont stages. This acute stiffening in late falciparum stages may contribute to fever-dependent pathological consequences in the microcirculation. Key words: deformability, magnetic twisting cytometry, erythrocyte, malaria.

PMID: 18596215 [PubMed - as supplied by publisher]

(Source: Am J Physiol Cell Ph...)

Neurokinin a engages neurokinin-1 receptor to induce nf-{kappa}b-dependent gene expression in murine macrophages: implications of erk1/2 and pi3k/akt pathways.

Am J Physiol Cell Ph... — Wed, 02 Jul 2008 04:00:00 +0100

Neurokinin A Engages Neurokinin-1 Receptor to Induce NF-{kappa}B-dependent Gene Expression in Murine Macrophages: Implications of ERK1/2 and PI3K/Akt Pathways.

Am J Physiol Cell Physiol. 2008 Jul 2;

Authors: Sun J, Ramnath RD, Tamizhselvi R, Bhatia M

Neurokinin A (NKA) belongs to the tachykinin neuropeptide family. Its biological functions are primarily mediated by the neurokinin (NK)-2 receptor. NKA has been implicated in several inflammatory conditions. However, there are limited data about the mechanism of its pathogenetic action. Here, we investigated proinflammatory effects of NKA on peripheral immune cells using a mouse macrophage/monocyte cell line RAW264.7 and primary peritoneal macrophages. The signaling mechanistic pathways involved was also studied. In mouse macrophages with no detectable NK-2 receptors, NKA induces the upregulation of NK-1 but not NK-2 receptor expression. Furthermore, NKA engages this NK-1 receptor resulting in inflammatory-like responses involving activation of the transcription factor NF-kappaB and induction of NF-kappaB-responsive proinflammatory chemokine expression. NKA activates NF-kappaB as evidenced by induced phosphorylation (leading to degradation) of its inhibitory protein IkappaBalpha, increased cellular levels of the transactivation-active phospho(Ser276)-p65 and its nuclear translocation, as well as enhanced DNA-binding activity of nuclear NF-kappaB. These responses are specifically inhibited by selective NK-1 receptor antagonists but not NK-2 receptor antagonists thereby excluding the role of NK-2 receptor. Further investigation on the upstream signaling mechanisms suggests two NF-kappaB-activating pathways ERK1/2 and PI3K/Akt are activated by NKA. Specific inhibitors of the two pathways block NF-kappaB-dependent chemokine expression. The inhibitory effects are mediated through regulation of nuclear translocation, DNA-binding activity and/or transactivation activity of NF-kappaB. Together, we provide novel evidence that NKA engages NK-1 receptors on mouse macrophages to elicit NF-kappaB-dependent cellular responses. The findings reveal cellular mechanisms that may underlie NKA-mediated inflammatory and immunological conditions. Key words: Neuroimmunomodulation, tachykinins, leukocytes, chemokines.

PMID: 18596216 [PubMed - as supplied by publisher]

(Source: Am J Physiol Cell Ph...)

All in one: leishmania major stt3 proteins substitute for the whole oligosaccharyltransferase complex in saccharomyces cerevisiae.

Mol Biol Cell — Wed, 02 Jul 2008 04:00:00 +0100

All in One: Leishmania major STT3 Proteins Substitute for the Whole Oligosaccharyltransferase Complex in Saccharomyces cerevisiae.

Mol Biol Cell. 2008 Jul 2;

Authors: Nasab FP, Schulz BL, Gamarro F, Parodi AJ, Aebi M

Monitoring Editor: Reid Gilmore The transfer of lipid-linked oligosaccharide to asparagine residues of polypeptide chains is catalyzed by oligosaccharyltransferase (OTase). In most eukaryotes, OTase is a hetero-oligomeric complex composed of eight different proteins, in which the STT3 component is believed to be the catalytic subunit. In the parasitic protozoa Leishmania major four STT3 paralogues, but no homologues to the other OTase components seem to be encoded in the genome. We expressed each of the four L. major STT3 proteins individually in S. cerevisiae and found that three of them, LmSTT3A, LmSTT3B, and LmSTT3D were able to complement a deletion of the yeast STT3 locus. Furthermore, LmSTT3D expression suppressed the lethal phenotype of single and double deletions in genes encoding other essential OTase subunits. LmSTT3 proteins did not incorporate into the yeast OTase complex but formed a homodimeric enzyme, capable of replacing the endogenous, multimeric enzyme of the yeast cell. Therefore, these protozoan OTases resemble the prokaryotic enzymes with respect to their architecture but they utilized substrates typical for eukaryotic cells: N-X-S/T sequons in proteins and dolicholpyrophosphate-linked high mannose oligosaccharides.

PMID: 18596231 [PubMed - as supplied by publisher]

(Source: Mol Biol Cell)