MedWorm: Biochemistry Top 20

Novel control of cAMP-regulated transcription in vascular endothelial cells.

Biochemical Society Transactions — Sun, 22 Jan 2012 22:32:39 +0100

Authors: Milne GR, Palmer TM, Yarwood SJ Abstract Chronic inflammatory diseases, such as atherosclerosis, are a major cause of death and disability in the developed world. In this respect, although cholesterol obviously plays a predominant role in atherosclerosis, targeting inflammation at lesion sites may be just as important. Indeed, elevated IL-6 (interleukin 6) levels are as strongly associated with coronary heart disease as increased cholesterol. We have been investigating novel cAMP-regulated pathways that combat the action of pro-inflammatory cytokines, such as IL-6 and leptin, in the VECs (vascular endothelial cells) of the circulatory system. In this respect, we have begun to unravel new molecular mechanisms by which the cAMP/Epac1 (exchange protein directly activated by c...

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Controlling cancer through the autotaxin-lysophosphatidic acid receptor axis.

Biochemical Society Transactions — Sun, 22 Jan 2012 22:31:40 +0100

Authors: Gotoh M, Fujiwara Y, Yue J, Liu J, Lee S, Fells J, Uchiyama A, Murakami-Murofushi K, Kennel S, Wall J, Patil R, Gupte R, Balazs L, Miller DD, Tigyi GJ Abstract LPA (lysophosphatidic acid, 1-acyl-2-hydroxy-sn-glycero-3-phosphate), is a growth factor-like lipid mediator that regulates many cellular functions, many of which are unique to malignantly transformed cells. The simple chemical structure of LPA and its profound effects in cancer cells has attracted the attention of the cancer therapeutics field and drives the development of therapeutics based on the LPA scaffold. In biological fluids, LPA is generated by ATX (autotaxin), a lysophospholipase D that cleaves the choline/serine headgroup from lysophosphatidylcholine and lysophosphatidylserine to generate LPA. In the pre...

Hydrocortisone attenuates cyclosporin A‐induced nephrotoxicity in rats

Journal of Cellular Biochemistry — Sat, 21 Jan 2012 18:16:06 +0100

This study clearly suggests the role of oxidative stress in the pathogenesis of CsA‐induced nephrotoxicity. J. Cell. Biochem. 113: 997–1004, 2012. © 2011 Wiley Periodicals, Inc. (Source: Journal of Cellular Biochemistry)

Putative roles for phospholipase Cη enzymes in neuronal Ca2+ signal modulation.

Biochemical Society Transactions — Sun, 22 Jan 2012 22:24:38 +0100

Authors: Popovics P, Stewart AJ Abstract The most recently identified PLC (phospholipase C) enzymes belong to the PLCη family. Their unique Ca2+-sensitivity and their specific appearance in neurons have attracted great attention since their discovery; however, their physiological role(s) in neurons are still yet to be established. PLCη enzymes are expressed in the neocortex, hippocampus and cerebellum. PLCη2 is also expressed at high levels in pituitary gland, pineal gland and in the retina. Driven by the specific localization of PLCη enzymes in different brain areas, in the present paper, we discuss the roles that they may play in neural processes, including differentiation, memory formation, circadian rhythm regulation, neurotransmitter/hormone release and the pathogenesis of...

Characterization and optimization of a simple, repeatable system for the long term in vitro culture of aligned myotubes in 3D

Journal of Cellular Biochemistry — Sat, 21 Jan 2012 18:16:13 +0100

AbstractIncreased recent research activity in exercise physiology has dramatically improved our understanding of skeletal muscle development and physiology in both health and disease. Advances in bioengineering have enabled the development of biomimetic 3D in vitro models of skeletal muscle which have the potential to further advance our understanding of the fundamental processes that underpin muscle physiology. As the principle structural protein of the extracellular matrix, collagen‐based matrices are popular tools for the creation of such 3D models but the custom nature of many reported systems has precluded their more widespread adoption. Here we present a simple, reproducible iteration of an established 3D in vitro model of skeletal muscle, demonstrating both the high levels of repr...

Decoding neurohormone pulse frequency by convergent signalling modules.

Biochemical Society Transactions — Sun, 22 Jan 2012 22:24:58 +0100

Authors: Tsaneva-Atanasova K, Caunt CJ, Armstrong SP, Perrett RM, McArdle CA Abstract GnRH (gonadotropin-releasing hormone) mediates control of reproduction. It is secreted in pulses and acts via intracellular effectors to activate gene expression. Submaximal GnRH pulse frequency can elicit maximal responses, yielding bell-shaped frequency-response curves characteristic of genuine frequency decoders. GnRH frequency decoding is therapeutically important (pulsatile GnRH can drive ovulation in assisted reproduction, whereas sustained activation can treat breast and prostate cancers), but the mechanisms are unknown. In the present paper, we review recent work in this area, placing emphasis on the regulation of transcription, and showing how mathematical modelling of GnRH effects on two...

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Structure of human tankyrase 1 in complex with small-molecule inhibitors PJ34 and XAV939

Acta Crystallographica Section F — Sat, 21 Jan 2012 18:18:26 +0100

The crystal structures of tankyrase 1 (TNKS1) in complex with two small-molecule inhibitors, PJ34 and XAV939, both at 2.0 Å resolution, are reported. The structure of TNKS1 in complex with PJ34 reveals two molecules of PJ34 bound in the NAD+ donor pocket. One molecule is in the nicotinamide portion of the pocket, as previously observed in other PARP structures, while the second molecule is bound in the adenosine portion of the pocket. Additionally, unlike the unliganded crystallization system, the TNKS1–PJ34 crystallization system has the NAD+ donor site accessible to bulk solvent in the crystal, which allows displacement soaking. The TNKS1–PJ34 crystallization system was used to determine the structure of TNKS1 in complex with XAV939. These structures provide a basis for the start ...

Editorial Board

FEBS Letters — Fri, 27 Jan 2012 18:32:03 +0100

(Source: FEBS Letters)

Physical and chemical aspects of stabilization of compounds in silk

Biopolymers — Tue, 24 Jan 2012 18:46:32 +0100

AbstractThe challenge of stabilization of small molecules and proteins has received considerable interest. The biological activity of small molecules can be lost as a consequence of chemical modifications, while protein activity may be lost due to chemical or structural degradation, such as a change in macromolecular conformation or aggregation. In these cases stabilization is required to preserve therapeutic and bioactivity efficacy and safety. In addition to use in therapeutic applications, strategies to stabilize small molecules and proteins also have applications in industrial processes, diagnostics, and consumer products like food and cosmetics. Traditionally, therapeutic drug formulation efforts have focused on maintaining stability during product preparation and storage. However, wi...

Neuropilin signalling in angiogenesis.

Biochemical Society Transactions — Sun, 22 Jan 2012 22:32:00 +0100

Authors: Koch S Abstract VEGFs (vascular endothelial growth factors) are master regulators of vascular development and of blood and lymphatic vessel function during health and disease in adults. This family of five mammalian ligands acts through three RTKs (receptor tyrosine kinases). In addition, co-receptors such as NRPs (neuropilins) associate with the ligand-receptor signalling complex and modulate the output. Therapeutics to block several of the VEGF signalling components as well as NRP function have been developed with the aim of halting blood vessel formation, angiogenesis, in diseases that involve tissue growth and inflammation, such as cancer. The present review outlines the current understanding of NRPs in relation to blood and lymphatic vessel biology. PMID: 22260660...

The Journal of Nutritional Biochemistry — Mon, 09 Jan 2012 22:10:52 +0100

(Source: The Journal of Nutritional Biochemistry)

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Targeting phosphoinositide 3-kinase δ for allergic asthma.

Biochemical Society Transactions — Sun, 22 Jan 2012 22:25:55 +0100

Authors: Rowan WC, Smith JL, Affleck K, Amour A Abstract Chronic inflammation in the lung has long been linked to the pathogenesis of asthma. Central to this airway inflammation is a T-cell response to allergens, with Th2 cytokines driving the differentiation, survival and function of the major inflammatory cells involved in the allergic cascade. PI3Kδ (phosphoinositide 3-kinase δ) is a lipid kinase, expressed predominantly in leucocytes, where it plays a critical role in immune receptor signalling. A selective PI3Kδ inhibitor is predicted to block T-cell activation in the lung, reducing the production of pro-inflammatory Th2 cytokines. PI3Kδ is also involved in B-cell and mast cell activation. Therefore the inhibition of PI3Kδ should dampen down the inflammatory cascade invol...

A novel and simple method of production and biophysical characterization of a mini‐membrane protein, Ost4p: A subunit of yeast oligosaccharyl transferase

Biopolymers — Fri, 03 Feb 2012 18:24:50 +0100

We report the cloning, successful overexpression and purification of recombinant Ost4p with a novel but simple method producing milligram quantities of pure protein. GB1 protein was found to be the most suitable tag for the large scale production of Ost4p. The cleavage of Ost4p conveniently leaves GB1 protein in solution eliminating further purification. The precipitated pure Ost4p is reconstituted in appropriate membrane mimetic. The recombinant protein is highly helical as indicated by the far‐UV CD spectrum. The well‐dispersed HSQC spectrum indicates that this minimembrane protein is well folded. The successful production of pure recombinant Ost4p with a novel yet simple method may have important ramification for the production of other membrane proteins. © 2012 Wiley Periodicals, ...

Proteomics analysis of in vitro protein methylation during Src‐induced transformation

Electrophoresis — Mon, 09 Jan 2012 05:00:00 +0100

In this study, we determined if protein methylation was involved in Src activation and which methylated proteins were associated with this activity. Using in vitro methylation and 2‐DE analysis of viral Src (v‐Src)‐transformed rat kidney epithelial cells (RK3E), several known and novel methylated proteins were identified based on their changes in methylation signal intensity upon transformation. Among these, elongation factor 2 (EF‐2), heterogeneous nuclear ribonucleoprotein K (hnRNP K), and β‐tubulin protein expressions remained unchanged, indicating that their altered methylation levels were due to Src activation. In addition, the altered expression of β‐actin, vimentin, and protein phosphatase 2, catalytic subunit (PPP2C) as well as protein phosphatase 2, catalytic subunit...

Tumor suppressor function of RUNX3 in breast cancer

Journal of Cellular Biochemistry — Mon, 23 Jan 2012 05:00:00 +0100

AbstractEmerging evidence indicates that RUNX3 is a tumor suppressor in breast cancer. RUNX3 is frequently inactivated in human breast cancer cell lines and cancer samples by hemizygous deletion of the Runx3 gene, hypermethylation of the Runx3 promoter, or cytoplasmic sequestration of RUNX3 protein. Inactivation of RUNX3 is associated with the initiation and progression of breast cancer. Female Runx3+/− mice spontaneously develop ductal carcinoma, and overexpression of RUNX3 inhibits the proliferation, tumorigenic potential, and invasiveness of breast cancer cells. This review is intended to summarize these findings and discuss the tumor suppressor function of RUNX3 in breast cancer. J. Cell. Biochem. © 2012 Wiley Periodicals, Inc. (Source: Journal of Cellular Biochemistry)

Editorial Board

FEBS Letters — Sun, 15 Jan 2012 07:34:02 +0100

(Source: FEBS Letters)

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Preface for the special issue of imaging brain aging and neurodegenerative disease.

Biochimica et Biophysica Acta — Sat, 28 Jan 2012 21:06:18 +0100

Authors: Gold BT, Keller JN PMID: 22265024 [PubMed - in process] (Source: Biochimica et Biophysica Acta)

Multi-pathway network analysis of mammalian epithelial cell responses in inflammatory environments.

Biochemical Society Transactions — Sun, 22 Jan 2012 22:28:54 +0100

Authors: Clarke DC, Lauffenburger DA Abstract Inflammation is a key physiological response to infection and injury and, although usually beneficial, it can also be damaging to the host. The liver is a prototypical example in this regard because inflammation helps to resolve liver injury, but it also underlies the aetiology of pathologies such as fibrosis and hepatocellular carcinoma. Liver cells sense their environment, including the inflammatory environment, through the activities of receptor-mediated signal transduction pathways. These pathways are organized in a complex interconnected network, and it is becoming increasingly recognized that cellular adaptations result from the quantitative integration of multi-pathway network activities, rather than isolated pathways causing par...

Heparan sulfate proteoglycans as multifunctional cell regulators: cell surface receptors.

Annual Review of Biochemistry — Mon, 23 Jan 2012 01:36:02 +0100

Authors: Li JP, Spillmann D Abstract Proteoglycans are macromolecules expressed on the cell surfaces and in the extracellular matrix of most animal tissues (Annu Rev Biochem 68:729-777, 1999; Int Rev Cell Mol Biol 276:105-159, 2009). Heparan sulfate proteoglycans (HSPGs) are essential for animal development and homeostasis, and are involved in various pathological processes. The functions of HSPGs are largely exerted through interaction of the heparan sulfate (HS) side chains with different types of ligands, including diverse molecules such as cytokines, enzymes, and pathogens. One of the important roles of cell surface HSPGs is to mediate cytokine-induced cell signaling through interaction with growth factors (GFs) and their cognate receptors. A selective dependence of GFs for dif...

Proteomic investigation of anti‐tumor activities exerted by sinularin against A2058 melanoma cells

Electrophoresis — Tue, 31 Jan 2012 05:00:00 +0100

The extracts from soft corals have been increasingly investigated for biomedical and therapeutic purposes. The aim of this study is to examine and analyze the anti‐tumor effects of the genus Sinularia extract sinularin on A2058 melanoma cells using MTT assay, cell migration assay, wound healing assay, flow cytometric analysis and proteomic analysis. Sinularin dose‐dependently (1∼5 μg/mL) inhibited melanoma cell proliferation while the treatment at identical concentrations suppressed cell migration. Sinularin dose‐dependently enhanced apoptotic melanoma cells and caused tumor cell accumulation at G2/M phase, indicating that sinularin exerts apoptosis‐induced and cell cycle‐delayed activities in A2058 melanoma cells. Comparative proteomic analysis was conducted to investigate th...

MedWorm: Biochemistry Top 20

Novel control of cAMP-regulated transcription in vascular endothelial cells.

Controlling cancer through the autotaxin-lysophosphatidic acid receptor axis.

Hydrocortisone attenuates cyclosporin A‐induced nephrotoxicity in rats

Putative roles for phospholipase Cη enzymes in neuronal Ca2+ signal modulation.

Characterization and optimization of a simple, repeatable system for the long term in vitro culture of aligned myotubes in 3D

Decoding neurohormone pulse frequency by convergent signalling modules.

Structure of human tankyrase 1 in complex with small-molecule inhibitors PJ34 and XAV939

Editorial Board

Physical and chemical aspects of stabilization of compounds in silk

Neuropilin signalling in angiogenesis.

Table of Contents

Targeting phosphoinositide 3-kinase δ for allergic asthma.

A novel and simple method of production and biophysical characterization of a mini‐membrane protein, Ost4p: A subunit of yeast oligosaccharyl transferase

Proteomics analysis of in vitro protein methylation during Src‐induced transformation

Tumor suppressor function of RUNX3 in breast cancer

Editorial Board

Preface for the special issue of imaging brain aging and neurodegenerative disease.

Multi-pathway network analysis of mammalian epithelial cell responses in inflammatory environments.

Heparan sulfate proteoglycans as multifunctional cell regulators: cell surface receptors.

Proteomic investigation of anti‐tumor activities exerted by sinularin against A2058 melanoma cells