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Selective and specific regulation of ectodomain shedding of angiotensin-converting enzyme 2 by tumor necrosis factor {alpha}-converting enzymeEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Angiotensin-converting enzyme 2 (ACE2) is a newly identified regulator of the renin-angiotensin system. This type I membrane-anchored protein has a catalytically active ectodomain that undergoes shedding. Tumor necrosis factor -converting enzyme (TACE) has been shown to be involved in ACE2 shedding. Although pathophysiological significance of ACE2 shedding has been suggested, regulation of this process by TACE is not clearly defined. We characterized TACE-mediated constitutive ectodomain shedding of ACE2 using wild-type Chinese Hamster Ovary (WT-CHO), the TACE-mutant M2 (M2-CHO) cells, and EC-4 and EC-2 cells that are fibr...
Source: AJP: Cell Physiology - October 29, 2009 Category: Cytology Authors: Iwata, M., Silva Enciso, J. E., Greenberg, B. H. Tags: CELLULAR AND MITOCHONDRIAL METABOLISM Source Type: journals

Inherent differences in morphology, proliferation, and migration in saphenous vein smooth muscle cells cultured from nondiabetic and Type 2 diabetic patientsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, SV-SMC from T2DM patients differ from nondiabetic SV-SMC in that they exhibit a rhomboid phenotype and are more migratory, but less proliferative, in response to serum. (Source: AJP: Cell Physiology)
Source: AJP: Cell Physiology - October 29, 2009 Category: Cytology Authors: Madi, H. A., Riches, K., Warburton, P., O'Regan, D. J., Turner, N. A., Porter, K. E. Tags: VASCULAR BIOLOGY Source Type: journals

Cholinergic agonists regulate JAK2/STAT3 signaling to suppress endothelial cell activationEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The cholinergic anti-inflammatory pathway is a physiological mechanism that inhibits cytokine production and minimizes tissue injury during inflammation. Previous investigations revealed that cholinergic stimulation (via cholinergic agonists and vagus nerve stimulation) suppresses endothelial cell activation and leukocyte recruitment. The purpose of this study was to investigate the mechanisms by which cholinergic agonists (e.g., nicotine and GTS-21) regulate endothelial cell activation. Specifically, we examined the effects of cholinergic agonists on IL-6-mediated endothelial cell activation through the JAK2/STAT3 signali...
Source: AJP: Cell Physiology - October 29, 2009 Category: Cytology Authors: Chatterjee, P. K., Al-Abed, Y., Sherry, B., Metz, C. N. Tags: VASCULAR BIOLOGY Source Type: journals

MEK, p38, and PI-3K mediate cross talk between EGFR and TNFR in enhancing hepatocyte growth factor production from human mesenchymal stem cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We reported previously that transforming growth factor- (TGF-), a putative mediator of wound healing and the injury response, increases the release of vascular endothelial growth factor (VEGF), augments tumor necrosis factor- (TNF-)-stimulated VEGF production, and activates mitogen-activated protein kinases and phosphatidylinositol 3-kinase (PI-3K) pathway in human MSCs. The experiments described in this report indicate that TGF- increases MSC-derived hepatocyte growth factor (HGF) production. TGF--stimulated HGF production was abolished by inhibition of MEK, p38, PI-3K, or by small interfering RNA (siRNA) targeting TNF re...
Source: AJP: Cell Physiology - October 29, 2009 Category: Cytology Authors: Wang, Y., Weil, B. R., Herrmann, J. L., Abarbanell, A. M., Tan, J., Markel, T. A., Kelly, M. L., Meldrum, D. R. Tags: RECEPTORS AND SIGNAL TRANSDUCTION Source Type: journals

Mind bomb 1 regulation of cFLIP interactionsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Mind bomb 1 (Mib1) is a multidomain E3 ligase that directs ubiquitination of the Notch ligands Delta and Jagged to promote their endocytosis. Here we examine Notch-independent functions of Mib1 and find that its activities are linked to the initiation of the extrinsic cell death pathway. Expression of Mib1 induces a spontaneous, caspase-dependent cell death. Consistent with this, depletion of endogenous Mib1 decreases tumor-necrosis factor (TNF)-induced cell death. Mib1 was found to bind to cellular Fas-associated death domain (FADD)-like IL-1b converting enzyme (FLICE)-like inhibitory proteins (cFLIP-L and cFLIP-S), where...
Source: AJP: Cell Physiology - October 29, 2009 Category: Cytology Authors: Zhang, L., Gallagher, P. J. Tags: RECEPTORS AND SIGNAL TRANSDUCTION Source Type: journals

Transforming growth factor-{beta}1 downregulates caveolin-1 expression and enhances sphingosine 1-phosphate signaling in cultured vascular endothelial cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We examined whether transforming growth factor-β1 (TGF-β1), a multifunctional cytokine, alters expression levels of caveolin-1 and influences heterologous receptor signaling. Treatment of cultured bovine aortic endothelial cells (BAEC) with TGF-β1 induces marked decreases in caveolin-1 expression in a time- and dose-dependent fashion at both levels of protein and mRNA. A pharmacological inhibitor of activin receptor-like kinase 5 (ALK-5) counteracts caveolin-1 downregulation by TGF-β1, indicating the involvement of ALK-5 receptor subtype for TGF-β1. Sphingosine 1-phosphate (S1P) is a serum-borne an...
Source: AJP: Cell Physiology - October 29, 2009 Category: Cytology Authors: Igarashi, J., Shoji, K., Hashimoto, T., Moriue, T., Yoneda, K., Takamura, T., Yamashita, T., Kubota, Y., Kosaka, H. Tags: RECEPTORS AND SIGNAL TRANSDUCTION Source Type: journals

17{beta}-Estradiol regulates the first steps of skeletal muscle cell differentiation via ER-{alpha}-mediated signalsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
17β-Estradiol (E2) mediates a wide variety of complex biological processes determining the growth and development of reproductive tract as well as nonreproductive tissues of male and female individuals. While E2 effects on the reproductive system, bone, and cardiovascular system are quite well established, less is known about how it affects the physiology of other tissues. Skeletal muscle is a tissue that is expected to be E2 responsive since both isoforms of estrogen receptor (ER- and ER-β) are expressed. Significant sex-related differences have been described in skeletal muscle, although the role played by E2 a...
Source: AJP: Cell Physiology - October 29, 2009 Category: Cytology Authors: Galluzzo, P., Rastelli, C., Bulzomi, P., Acconcia, F., Pallottini, V., Marino, M. Tags: RECEPTORS AND SIGNAL TRANSDUCTION Source Type: journals

Closed-state inactivation in Kv4.3 isoforms is differentially modulated by protein kinase CEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Kv4.3, with its complex open- and closed-state inactivation (CSI) characteristics, is a primary contributor to early cardiac repolarization. The two alternatively spliced forms, Kv4.3-short (Kv4.3-S) and Kv4.3-long (Kv4.3-L), differ by the presence of a 19-amino acid insert downstream from the sixth transmembrane segment. The isoforms are similar kinetically; however, the longer form has a unique PKC phosphorylation site. To test the possibility that inactivation is differentially regulated by phosphorylation, we expressed the Kv4.3 isoforms in Xenopus oocytes and examined changes in their inactivation properties after sti...
Source: AJP: Cell Physiology - October 29, 2009 Category: Cytology Authors: Xie, C., Bondarenko, V. E., Morales, M. J., Strauss, H. C. Tags: MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS Source Type: journals

IL-6 stimulates system A amino acid transporter activity in trophoblast cells through STAT3 and increased expression of SNAT2Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, we have identified a novel regulatory pathway involving increased gene expression of the SNAT2 isoform mediated by a STAT-dependent pathway, which links IL-6 to increased activity of system A, a ubiquitously expressed transporter of neutral amino acids. From these new findings, we propose that upregulation of amino acid transporters by cytokines may contribute to increased placental nutrient transport and fetal overgrowth, which are commonly found in pregnancies complicated by maternal diabetes and obesity. (Source: AJP: Cell Physiology)
Source: AJP: Cell Physiology - October 29, 2009 Category: Cytology Authors: Jones, H. N., Jansson, T., Powell, T. L. Tags: MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS Source Type: journals

Hepatocyte nuclear factor 1 is essential for transcription of sodium-dependent vitamin C transporter protein 1Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we present the first investigation of the transcriptional regulation of human Slc23a1, identifying transcription factors that may influence its expression. A 1,239-bp genomic DNA fragment corresponding to the 5'-flanking region of Slc23a1 was isolated from a human hepatocarcinoma cell line (HepG2) and sequenced. When cloned into a reporter gene construct, robust transcriptional activity was seen in this sequence, nearly 25-fold above the control vector. Deletion analysis of the SVCT1 reporter gene vector defined the minimal active promoter as a small 135-bp region upstream of the transcriptional start site. ...
Source: AJP: Cell Physiology - October 29, 2009 Category: Cytology Authors: Michels, A. J., Hagen, T. M. Tags: MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS Source Type: journals

The mechanical behavior of individual sarcomeres of myofibrils isolated from rabbit psoas muscleEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The goal of this study was to develop a system to experiment with sarcomeres mechanically isolated from skeletal muscles. Single myofibrils from rabbit psoas were transferred into a temperature-controlled (22°C or 15°C) experimental chamber, and sarcomeres were isolated using precalibrated glass microneedles that were pierced externally, adjacent to the Z-lines. The force produced during activation was measured by tracking the displacement of the microneedles, and the sarcomere and half-sarcomere changes were measured by continuously tracking the Z-lines and A-bands position during the experiments. Sarcomeres produ...
Source: AJP: Cell Physiology - October 29, 2009 Category: Cytology Authors: Pavlov, I., Novinger, R., Rassier, D. E. Tags: METHODS IN CELL PHYSIOLOGY Source Type: journals

Molecular regulation of cigarette smoke induced-oxidative stress in human retinal pigment epithelial cells: implications for age-related macular degenerationEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study investigated the molecular and cellular effects of cigarette smoke exposure on human RPE cells. ARPE-19 or primary human RPE cells were exposed to cigarette smoke extract (CSE) or hydroquinone (HQ), a component of cigarette smoke. The effect of this exposure on key aspects of RPE vitality including viability, cell size, mitochondrial membrane potential (m), superoxide production, 4-hydroxy-2-nonenal (4-HNE), vascular endothelial growth factor (VEGF), and heme oxygenase-1 (HO-1) expression was determined. Exposure of RPE cells to CSE or HQ caused oxidative damage and apoptosis, characterized by a reduction in cel...
Source: AJP: Cell Physiology - October 29, 2009 Category: Cytology Authors: Bertram, K. M., Baglole, C. J., Phipps, R. P., Libby, R. T. Tags: NERVOUS SYSTEM CELL BIOLOGY Source Type: journals

Influence of zinc deficiency on Akt-Mdm2-p53 and Akt-p21 signaling axes in normal and malignant human prostate cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Phosphorylated Akt (p-Akt), a phosphoinositide-3-OH-kinase-activated protein kinase, is highly expressed in prostate tumors. p-Akt can indirectly hinder p53-dependent growth suppression and apoptosis by phosphorylating Mdm2. Alternatively, p-Akt can directly phosphorylate p21 and restrict it to the cytoplasm for degradation. Because the prostate is the highest zinc-accumulating tissue before the onset of cancer, the effects of physiological levels of zinc on Akt-Mdm2-p53 and Akt-p21 signaling axes in human normal prostate epithelial cells (PrEC) and malignant prostate LNCaP cells were examined in the present study. Cells w...
Source: AJP: Cell Physiology - October 29, 2009 Category: Cytology Authors: Han, C.-T., Schoene, N. W., Lei, K. Y. Tags: CELLULAR AND MITOCHONDRIAL METABOLISM Source Type: journals

Estradiol-mediated ERK phosphorylation and apoptosis in vascular smooth muscle cells requires GPR 30Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Recent studies suggest that the rapid and nongenomic effects of estradiol may be mediated through the G protein-coupled receptor dubbed GPR30 receptor. The present study examines the role of GPR30 versus a classical estrogen receptor (ER) in mediating the growth regulatory effects of estradiol. GPR30 is readily detectable in freshly isolated vascular tissue but barely detectable in cultured vascular smooth muscle cells (VSMC). In freshly isolated aortic tissue, estradiol stimulated extracellular signal-regulated kinases (ERK) phosphorylation. In contrast, in cultured VSMC, where GPR30 expression is significantly reduced, e...
Source: AJP: Cell Physiology - October 29, 2009 Category: Cytology Authors: Ding, Q., Gros, R., Limbird, L. E., Chorazyczewski, J., Feldman, R. D. Tags: GROWTH, DIFFERENTIATION, AND APOPTOSIS Source Type: journals

T-cadherin is located in the nucleus and centrosomes in endothelial cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We examined T-cadherin location in human endothelial cells using confocal microscopy and subcellular fractionation. We found that a considerable proportion of T-cadherin is located in the nucleus and in the centrosomes. T-cadherin colocalized with a centrosomal marker -tubulin uniformly throughout the cell cycle at least in human umbilical vein endothelial cells. In the telophase, T-cadherin transiently concentrated in the midbody and was apparently degraded. Its overexpression resulted in an increase in the number of multinuclear cells, whereas its downregulation by small interfering RNA led to an increase in the number o...
Source: AJP: Cell Physiology - October 29, 2009 Category: Cytology Authors: Andreeva, A. V., Kutuzov, M. A., Tkachuk, V. A., Voyno-Yasenetskaya, T. A. Tags: VASCULAR BIOLOGY Source Type: journals

The C type natriuretic peptide receptor tethers AHNAK1 at the plasma membrane to potentiate arachidonic acid-induced calcium mobilizationEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Arachidonic acid (AA) liberated from membrane phospholipids is known to activate phospholipase C 1 (PLC1) concurrently with AHNAK in nonneuronal cells. The recruitment of AHNAK from the nucleus is required for it to activate PLC1 at the plasma membrane. Here, we identify the C-type natriuretic peptide receptor (NPR-C), an atypical G protein-coupled receptor, as a protein binding partner for AHNAK1 in various cell types. Mass spectrometry and MASCOT analysis of excised bands from NPR-C immunoprecipitation studies revealed multiple signature peptides corresponding to AHNAK1. Glutathione S-transferase (GST) pulldown assays us...
Source: AJP: Cell Physiology - October 29, 2009 Category: Cytology Authors: Alli, A. A., Gower, W. R. Tags: RECEPTORS AND SIGNAL TRANSDUCTION Source Type: journals

Retinoic acid-induced nNOS expression depends on a novel PI3K/Akt/DAX1 pathway in human TGW-nu-I neuroblastoma cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Neuronal nitric oxide synthase (nNOS)-derived nitric oxide (NO) acts as a neurotransmitter and intracellular signaling molecule in the central and peripheral nervous system. NO regulates multiple processes like neuronal development, plasticity, and differentiation and is a mediator of neurotoxicity. The nNOS gene is highly complex with 12 alternative first exons, exon 1a–1l, transcribed from distinct promoters, leading to nNOS variants with different 5'-untranslated regions. Transcriptional control of the nNOS gene is not understood in detail. To investigate regulation of nNOS gene expression by retinoic acid (RA), w...
Source: AJP: Cell Physiology - October 29, 2009 Category: Cytology Authors: Nagl, F., Schonhofer, K., Seidler, B., Mages, J., Allescher, H.-D., Schmid, R. M., Schneider, G., Saur, D. Tags: RECEPTORS AND SIGNAL TRANSDUCTION Source Type: journals

Negative modulation of inositol 1,4,5-trisphosphate type 1 receptor expression prevents dystrophin-deficient muscle cells deathEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Evidence for a modulatory effect of cyclosporin A (CsA) on calcium signaling and cell survival in dystrophin-deficient cells is presented. Our previous works strongly supported the hypothesis of an overactivation of Ca2+ release via inositol 1,4,5-trisphosphate (IP3) receptors (IP3R) in dystrophin-deficient cells, both during membrane depolarization and at rest, through spontaneous Ca2+ release events. Forced expression of mini-dystrophin in these cells contributed, during stimulation and in resting condition, to the recovery of a controlled calcium homeostasis. In the present work, we demonstrate that CsA exposure display...
Source: AJP: Cell Physiology - October 29, 2009 Category: Cytology Authors: Mondin, L., Balghi, H., Constantin, B., Cognard, C., Sebille, S. Tags: MUSCLE CELL BIOLOGY AND CELL MOTILITY Source Type: journals

Myostatin inhibits IGF-I-induced myotube hypertrophy through AktEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We examined the functional role of myostatin modulation of Akt in C2C12 myotubes, a well-established in vitro model of skeletal muscle hypertrophy. Adenoviral overexpression of myostatin attenuated the insulin-like growth factor-I (IGF-I)-mediated increase in myotube diameter, as well as IGF-I-stimulated Akt phosphorylation. Inhibition of myostatin by overexpression of the NH2-terminal portion of myostatin was sufficient to increase myotube diameter and Akt phosphorylation. Coexpression of myostatin and constitutively active Akt (myr-Akt) restored the increase in myotube diameter. Conversely, expression of dominant negativ...
Source: AJP: Cell Physiology - October 29, 2009 Category: Cytology Authors: Morissette, M. R., Cook, S. A., Buranasombati, C., Rosenberg, M. A., Rosenzweig, A. Tags: MUSCLE CELL BIOLOGY AND CELL MOTILITY Source Type: journals

Identification of Sp1 and GC-boxes as transcriptional regulators of mouse Dag1 gene promoterEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, for the first time we have characterized the activity of the mouse Dag1 gene promoter, confirming a complex regulation by Sp1 transcription factor, DNA methylation, and histone acetylation, which might be relevant for a better understanding of the physiopathology of the dystroglycan complex. (Source: AJP: Cell Physiology)
Source: AJP: Cell Physiology - October 29, 2009 Category: Cytology Authors: Rettino, A., Rafanelli, F., Genovese, G., Goracci, M., Cifarelli, R. A., Cittadini, A., Sgambato, A. Tags: MUSCLE CELL BIOLOGY AND CELL MOTILITY Source Type: journals

Orai1, a critical component of store-operated Ca2+ entry, is functionally associated with Na+/Ca2+ exchanger and plasma membrane Ca2+ pump in proliferating human arterial myocytesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Ca2+ entry through store-operated channels (SOCs) in the plasma membrane plays an important role in regulation of vascular smooth muscle contraction, tone, and cell proliferation. The C-type transient receptor potential (TRPC) channels have been proposed as major candidates for SOCs in vascular smooth muscle. Recently, two families of transmembrane proteins, Orai [also known as Ca2+ release-activated Ca2+ channel modulator (CRACM)] and stromal interacting molecule 1 (STIM1), were shown to be essential for the activation of SOCs mainly in nonexcitable cells. Here, using small interfering RNA, we show that Orai1 plays an ess...
Source: AJP: Cell Physiology - October 29, 2009 Category: Cytology Authors: Baryshnikov, S. G., Pulina, M. V., Zulian, A., Linde, C. I., Golovina, V. A. Tags: MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS Source Type: journals

Bicarbonate homeostasis in excitable tissues: role of AE3 Cl-/HCOFormula exchanger and carbonic anhydrase XIV interactionEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Bicarbonate transport and metabolism are key elements of normal cellular function. Two alternate transcripts of anion exchanger 3 (AE3), full-length (AE3fl) and cardiac (AE3c), are expressed in central nervous system (CNS), where AE3 catalyzes electroneutral Cl–/HCO3– exchange across the plasma membrane of neuronal and glial cells of CNS. Anion exchanger isoforms, AE3fl and AE3c, associate with the carbonic anhydrases (CA) CAII and CAIV, forming a HCO3– transport metabolon, to maximize HCO3– flux across the plasma membrane. CAXIV, with catalytic domain anchored to the extracellular surface, is also ...
Source: AJP: Cell Physiology - October 29, 2009 Category: Cytology Authors: Casey, J. R., Sly, W. S., Shah, G. N., Alvarez, B. V. Tags: MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS Source Type: journals

An environmental sensor, TRPV4 is a novel regulator of intracellular Ca2+ in human synoviocytesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we provide evidence that TRPV4 is a functional regulator of Ca2+i in human synoviocytes. Although significant expression of TRPV4 in synoviocytes from patients with (RA) and without (CTR) rheumatoid arthritis was detected at mRNA and protein level, those in the human fibroblast-like synoviocyte line MH7A were rather lower. Consistently, the selective TRPV4 agonist 4-phorbol 12,13-didecanoate (4PDD) effectively elevated Ca2+i in the RA and CTR cells, which was abolished by the removal of external Ca2+. Moreover, the elevation was inhibited by ruthenium red, a blocker of TRPVs. In MH7A cells transfected with h...
Source: AJP: Cell Physiology - October 29, 2009 Category: Cytology Authors: Itoh, Y., Hatano, N., Hayashi, H., Onozaki, K., Miyazawa, K., Muraki, K. Tags: MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS Source Type: journals

Loss of the apical V-ATPase a-subunit VHA-6 prevents acidification of the intestinal lumen during a rhythmic behavior in C. elegansEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In Caenorhabditis elegans, oscillations of intestinal pH contribute to the rhythmic defecation behavior, but the acid-base transport mechanisms that facilitate proton movement are not well understood. Here, we demonstrate that VHA-6, an intestine-specific a-subunit of the H+-K+-ATPase complex (V-ATPase), resides in the apical membrane of the intestinal epithelial cells and is required for luminal acidification. Disruption of the vha-6 gene led to early developmental arrest; the arrest phenotype could be complemented by expression of a fluorescently labeled vha-6 transgene. To study the contribution of vha-6 to pH homeostas...
Source: AJP: Cell Physiology - October 29, 2009 Category: Cytology Authors: Allman, E., Johnson, D., Nehrke, K. Tags: MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS Source Type: journals

Angiotensin II induces RhoA activation through SHP2-dependent dephosphorylation of the RhoGAP p190A in vascular smooth muscle cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Angiotensin II (ANG II) is a major regulator of blood pressure that essentially acts through activation of ANG II type 1 receptor (AT1R) of vascular smooth muscle cells (VSMC). AT1R activates numerous intracellular signaling pathways, including the small G protein RhoA known to control several VSMC functions. Nevertheless, the mechanisms leading to RhoA activation by AT1R are unknown. RhoA activation can result from activation of RhoA exchange factor and/or inhibition of Rho GTPase-activating protein (GAP). Here we hypothesize that a RhoGAP could participate to RhoA activation induced by ANG II in rat aortic VSMC. The knoc...
Source: AJP: Cell Physiology - October 29, 2009 Category: Cytology Authors: Bregeon, J., Loirand, G., Pacaud, P., Rolli-Derkinderen, M. Tags: RECEPTORS AND SIGNAL TRANSDUCTION Source Type: journals

Angiotensin II type-1 receptor regulates RhoA and Rho-kinase/ROCK activation via multiple mechanisms. Focus on "Angiotensin II induces RhoA activation through SHP2-dependent dephosphorylation of the RhoGAP p190A in vascular smooth muscle cells"Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
(Source: AJP: Cell Physiology)
Source: AJP: Cell Physiology - October 29, 2009 Category: Cytology Authors: Kimura, K., Eguchi, S. Tags: EDITORIAL FOCUS Source Type: journals

Rab34 and its effector munc13-2 constitute a new pathway modulating protein secretion in the cellular response to hyperglycemiaEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Diabetic nephropathy (DN) is the leading cause of end-stage renal disease requiring dialysis in the Western world. Clinical studies reveal that stringent control of blood glucose levels reduces the risk of most diabetic complications, underscoring the importance of understanding the cellular response to hyperglycemia. Our work identifies a new pathway of potential significance in this response, linking hyperglycemia to the stimulation of constitutive protein secretion via a pathway involving munc13 and rab34. These two proteins have previously been shown to interact at the Golgi via the munc13 homology domain 2 (MHD2). In ...
Source: AJP: Cell Physiology - October 1, 2009 Category: Cytology Authors: Goldenberg, N. M., Silverman, M. Tags: PROTEIN AND VESICLE TRAFFICKING, CYTOSKELETON Source Type: journals

A-769662 activates AMPK {beta}1-containing complexes but induces glucose uptake through a PI3-kinase-dependent pathway in mouse skeletal muscleEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
5'-AMP-activated protein kinase (AMPK) regulates several aspects of metabolism. Recently, A-769662 was shown to activate AMPK in skeletal muscle. However, no biological effects of AMPK activation by A-769662 in this tissue have been reported. We hypothesized that A-769662 would increase glucose uptake in skeletal muscle. We studied incubated soleus and extensor digitorum longus (EDL) muscles from 129S6/sv and C57BL/6 mice. Glucose uptake increased only in soleus from 129S6/sv when concentrations of A-769662 were 500 µM (~15%, P < 0.05) and 1 mM (~60%, P < 0.01). AMPK β1- but not β2-containing complexe...
Source: AJP: Cell Physiology - October 1, 2009 Category: Cytology Authors: Treebak, J. T., Birk, J. B., Hansen, B. F., Olsen, G. S., Wojtaszewski, J. F. P. Tags: RECEPTORS AND SIGNAL TRANSDUCTION Source Type: journals

Functional characterization of two isoforms of the P2Y-like receptor GPR17: [35S]GTP{gamma}S binding and electrophysiological studies in 1321N1 cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The previously "orphan" G protein-coupled receptor GPR17 is structurally related to both P2Y nucleotide receptors and to receptors for cysteinyl leukotrienes. Genomic analysis revealed two putative open reading frames encoding for a "short" and a "long" receptor isoform of 339- and 367-amino acids, respectively, with the latter displaying a 28-amino acid longer NH2 terminus. The short isoform has been recently "deorphanized," revealing dual responses to uracil nucleotides and cysteinyl leukotrienes. No information regarding the ligand specificity, tissue distribution, or pathophysiological roles of the long receptor isofor...
Source: AJP: Cell Physiology - October 1, 2009 Category: Cytology Authors: Pugliese, A. M., Trincavelli, M. L., Lecca, D., Coppi, E., Fumagalli, M., Ferrario, S., Failli, P., Daniele, S., Martini, C., Pedata, F., Abbracchio, M. P. Tags: RECEPTORS AND SIGNAL TRANSDUCTION Source Type: journals

IGF-I activates the mouse type IIb myosin heavy chain geneEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
IGF-I increases skeletal muscle mass, but whether IGF-I increases type IIb myosin heavy chain (MyHC) transcriptional activity is not known. C2C12 myotubes were cultured with or without IGF-I to determine whether IGF-I increases type IIb MyHC promoter activity, and if so, what region of the promoter might IGF-I signaling regulate. At differentiation days 3 and 4, IGF-I increased type IIb MyHC mRNA and mouse 3.0-kb type IIb MyHC promoter activity. Deletion construct studies identified a potential IGF-I-responsive region between 1.25 and 1.2 kb of the type IIb MyHC promoter, which contained an exact 6-bp T-cell factor/lymphoi...
Source: AJP: Cell Physiology - October 1, 2009 Category: Cytology Authors: Shanely, R. A., Zwetsloot, K. A., Childs, T. E., Lees, S. J., Tsika, R. W., Booth, F. W. Tags: MUSCLE CELL BIOLOGY AND CELL MOTILITY Source Type: journals

Different roles of H-ras for regulation of myosin heavy chain promoters in satellite cell-derived muscle cell culture during proliferation and differentiationEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The effect of constitutively activated proto-oncogene H-ras (H-rasQ61L) on the regulation of myosin heavy chain (MHC) promoter activities was investigated in rabbit satellite cell-derived muscle cell culture during the proliferation stage and early and later stages of differentiation, respectively. During proliferation, overexpression of H-rasQ61L did not affect basal level of activity of the slow MHCI/β or the fast MHCIId/x promoter luciferase reporter gene construct in transient transfection assays. By contrast, H-rasQ61L affected both MHC promoter activities during differentiation, and this effect changes from inac...
Source: AJP: Cell Physiology - October 1, 2009 Category: Cytology Authors: Scholz, M. E., Meissner, J. D., Scheibe, R. J., Umeda, P. K., Chang, K.-C., Gros, G., Kubis, H.-P. Tags: MUSCLE CELL BIOLOGY AND CELL MOTILITY Source Type: journals

Regulation of Kir channels in bovine retinal pigment epithelial cells by phosphatidylinositol 4,5-bisphosphateEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The inwardly rectifying K+ (Kir) current in mammalian retinal pigment epithelial (RPE) cells, which is largely mediated by Kir7.1 channels, is stable in cells dialyzed with MgATP but runs down when intracellular ATP is depleted. A potential mechanism for this rundown is a decrease in phosphatidylinositol 4,5-bisphosphate (PIP2) regeneration by ATP-dependent lipid kinases. Here, we used the whole cell voltage-clamp technique to investigate the membrane PIP2 dependence of Kir channels in isolated bovine RPE cells. When RPE cells were dialyzed with ATP-free solution containing PIP2 (25–50 µM), rundown persisted bu...
Source: AJP: Cell Physiology - October 1, 2009 Category: Cytology Authors: Pattnaik, B. R., Hughes, B. A. Tags: MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS Source Type: journals

Activation of maxi-anion channel by protein tyrosine dephosphorylationEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The maxi-anion channel with a large single-channel conductance of >300 pS, and unknown molecular identity, is functionally expressed in a large variety of cell types. The channel is activated by a number of experimental maneuvers such as exposing cells to hypotonic or ischemic stress. The most effective and consistent method of activating it is patch membrane excision. However, the activation mechanism of the maxi-anion channel remains poorly understood at present. In the present study, involvement of phosphorylation/dephosphorylation in excision-induced activation was examined. In mouse mammary fibroblastic C127 cells,...
Source: AJP: Cell Physiology - October 1, 2009 Category: Cytology Authors: Toychiev, A. H., Sabirov, R. Z., Takahashi, N., Ando-Akatsuka, Y., Liu, H., Shintani, T., Noda, M., Okada, Y. Tags: MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS Source Type: journals

Secretory state regulates Zn2+ transport in gastric parietal cell of the rabbitEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Secretory compartments of neurons, endocrine cells, and exocrine glands are acidic and contain high levels of labile Zn2+. Previously, we reported evidence that acidity is regulated, in part, by the content of Zn2+ in the secretory [i.e., tubulovesicle (TV)] compartment of the acid-secreting gastric parietal cell. Here we report studies focusing on the mechanisms of Zn2+ transport by the TV compartment in the mammalian (rabbit) gastric parietal cell. Uptake of Zn2+ by isolated TV structures was monitored with a novel application of the fluorescent Zn2+ reporter N-(6-methoxy-8-quinolyl)-para-toluenesulfonamide (TSQ). Uptake...
Source: AJP: Cell Physiology - October 1, 2009 Category: Cytology Authors: Naik, H. B., Beshire, M., Walsh, B. M., Liu, J., Soybel, D. I. Tags: MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS Source Type: journals

Caffeine inhibits nonselective cationic currents in interstitial cells of Cajal from the murine jejunumEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Interstitial cells of Cajal (ICC) discharge unitary potentials in gastrointestinal muscles that constitute the basis for pacemaker activity. Caffeine has been used to block unitary potentials, but the ionic conductance responsible for unitary potentials is controversial. We investigated currents in cultured ICC from murine jejunum that may underlie unitary potentials and studied the effects of caffeine. Networks of ICC generated slow wave events under current clamp, and these events were blocked by caffeine in a concentration-dependent manner. Single ICC generated spontaneous transient inward currents (STICs) under voltage...
Source: AJP: Cell Physiology - October 1, 2009 Category: Cytology Authors: Jin, N. G., Koh, S. D., Sanders, K. M. Tags: MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS Source Type: journals

Augmentation of Cav1 channel current and action potential duration after uptake of S100A1 in sympathetic ganglion neuronsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
S100A1, a 21-kDa dimeric Ca2+-binding protein of the EF-hand type, is expressed in cardiomyocytes and is an important regulator of heart function. During ischemia, cardiomyocytes secrete S100A1 to the extracellular space. Although the effects of extracellular S100A1 have been documented in cardiomyocytes, it is unclear whether S100A1 exerts modulatory effects on other tissues in proximity with cardiac cells. Therefore, we sought to investigate the effects of exogenous S100A1 on Ca2+ signals and electrical properties of superior cervical ganglion (SCG) neurons. Immunostaining and Western blot assays indicated no endogenous ...
Source: AJP: Cell Physiology - October 1, 2009 Category: Cytology Authors: Hernandez-Ochoa, E. O., Prosser, B. L., Wright, N. T., Contreras, M., Weber, D. J., Schneider, M. F. Tags: NERVOUS SYSTEM CELL BIOLOGY Source Type: journals

Endothelial barrier protection by FTY720 under hyperglycemic condition: involvement of focal adhesion kinase, small GTPases, and adherens junction proteinsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Recently, sphingosine 1-phosphate (S1P) has been highlighted as an endothelial barrier-stabilizing mediator. FTY720 is a S1P analog originally developed as a novel immunosuppressant. The phosphorylated form of FTY720 binds to S1P receptors to exert S1P-like biological effects, suggesting endothelial barrier promotion by FTY720. To elucidate whether FTY720 induces signaling events related to endothelial barrier enhancement under hyperglycemic conditions, human microvascular endothelial cells (HMVECs) preincubated with hyperglycemic (30 mM) medium were treated with 100 nM FTY720 for 3 h. Immunofluorescent microscopy and copr...
Source: AJP: Cell Physiology - October 1, 2009 Category: Cytology Authors: Sarai, K., Shikata, K., Shikata, Y., Omori, K., Watanabe, N., Sasaki, M., Nishishita, S., Wada, J., Goda, N., Kataoka, N., Makino, H. Tags: EXTRACELLULAR MATRIX, CELL INTERACTIONS Source Type: journals

Caveolin-1 plays important role in EGF-induced migration and proliferation of mouse embryonic stem cells: involvement of PI3K/Akt and ERKEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, these results demonstrated that EGF-induced DNA synthesis and cell migration are mediated by caveolin-1, which is activated by Src, FAK, PI3K/Akt, ERK, and MMP-2 signals in mouse ES cells. (Source: AJP: Cell Physiology)
Source: AJP: Cell Physiology - October 1, 2009 Category: Cytology Authors: Park, J. H., Han, H. J. Tags: GROWTH, DIFFERENTIATION, AND APOPTOSIS Source Type: journals

Cytochrome c oxidase III as a mechanism for apoptosis in heart failure following myocardial infarctionEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Cytochrome c oxidase (COX) is composed of 13 subunits, of which COX I, II, and III are encoded by a mitochondrial gene. COX I and II function as the main catalytic components, but the function of COX III is unclear. Because myocardial ischemia affects mitochondrial oxidative metabolism, we hypothesized that COX activity and expression would be affected during postischemic cardiomyopathy. This hypothesis was tested in a monkey model following myocardial infarction (MI) and subsequent pacing-induced heart failure (HF). In this model, COX I protein expression was decreased threefold after MI and fourfold after HF (P < 0.05...
Source: AJP: Cell Physiology - October 1, 2009 Category: Cytology Authors: Wu, C., Yan, L., Depre, C., Dhar, S. K., Shen, Y.-T., Sadoshima, J., Vatner, S. F., Vatner, D. E. Tags: GROWTH, DIFFERENTIATION, AND APOPTOSIS Source Type: journals

The mechanism of opiorphin-induced experimental priapism in rats involves activation of the polyamine synthetic pathwayEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Intracorporal injection of plasmids encoding opiorphins into retired breeder rats can result in animals developing a priapic-like condition. Microarray analysis demonstrated that following intracorporal gene transfer of plasmids expressing opiorphins the most significantly upregulated gene in corporal tissue was the ornithine decarboxylase gene (ODC). Quantitative RT-PCR confirmed the upregulation of ODC, as well as other genes involved in polyamine synthesis, such as arginase-I and -II, polyamine oxidase, spermidine synthase, spermidine acetyltransferase (SAT), and S-adenosylmethionine decarboxylase. Western blot analysis...
Source: AJP: Cell Physiology - October 1, 2009 Category: Cytology Authors: Kanika, N. D., Tar, M., Tong, Y., Kuppam, D. S. R., Melman, A., Davies, K. P. Tags: VASCULAR BIOLOGY Source Type: journals

Hypochlorous acid-induced heme oxygenase-1 gene expression promotes human endothelial cell survivalEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Hypochlorous acid (HOCl) is a unique oxidant generated by the enzyme myeloperoxidase that contributes to endothelial cell dysfunction and death in atherosclerosis. Since myeloperoxidase localizes with heme oxygenase-1 (HO-1) in and around endothelial cells of atherosclerotic lesions, the present study investigated whether there was an interaction between these two enzymes in vascular endothelium. Treatment of human endothelial cells with the myeloperoxidase product HOCl stimulated a concentration- and time-dependent increase in HO-1 protein that resulted in a significant rise in carbon monoxide (CO) production. The inducti...
Source: AJP: Cell Physiology - October 1, 2009 Category: Cytology Authors: Wei, Y., Liu, X.-m., Peyton, K. J., Wang, H., Johnson, F. K., Johnson, R. A., Durante, W. Tags: VASCULAR BIOLOGY Source Type: journals

Hyperosmolarity regulates SOX9 mRNA posttranscriptionally in human articular chondrocytesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study we investigated whether regulation of p38 MAPK caused by changes in osmotic pressure could control SOX9 mRNA levels expression by a similar mechanism. Primary human articular chondrocytes isolated from osteoarthritic cartilage at passage 2-4 showed significantly raised SOX9 mRNA levels when exposed to hyperosmotic conditions for 5 h. The effect was strongest and most reproducible when actin stress fibers were disrupted by the Rho effector kinase inhibitor Y27632, or by culturing the cells within alginate beads. Freshly isolated chondrocytes, used within 24–48 h of isolation, did not contain actin stress...
Source: AJP: Cell Physiology - October 1, 2009 Category: Cytology Authors: Tew, S. R., Peffers, M. J., McKay, T. R., Lowe, E. T., Khan, W. S., Hardingham, T. E., Clegg, P. D. Tags: RECEPTORS AND SIGNAL TRANSDUCTION Source Type: journals

Amantadine inhibits platelet-activating factor induced clathrin-mediated endocytosis in human neutrophilsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Receptor signaling is integral for adhesion, emigration, phagocytosis, and reactive oxygen species production in polymorphonuclear neutrophils (PMNs). Priming is an important part of PMN emigration, but it can also lead to PMN-mediated organ injury in the host. Platelet-activating factor (PAF) primes PMNs through activation of a specific G protein-coupled receptor. We hypothesize that PAF priming of PMNs requires clathrin-mediated endocytosis (CME) of the PAF receptor (PAFr), and, therefore, amantadine, known to inhibit CME, significantly antagonizes PAF signaling. PMNs were isolated by standard techniques to >98% purit...
Source: AJP: Cell Physiology - October 1, 2009 Category: Cytology Authors: Eckels, P. C., Banerjee, A., Moore, E. E., McLaughlin, N. J. D., Gries, L. M., Kelher, M. R., England, K. M., Gamboni-Robertson, F., Khan, S. Y., Silliman, C. C. Tags: RECEPTORS AND SIGNAL TRANSDUCTION Source Type: journals

Mechanisms underlying Andersen's syndrome pathology in skeletal muscle are revealed in human myotubesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Andersen's syndrome is a rare disorder that has been defined with a triad: periodic paralysis, cardiac arrhythmia, and development anomalies. Muscle weakness has been reported in two-thirds of the patients. KCNJ2 remains the only gene linked to Andersen's syndrome; this gene encodes for the -subunit of the strong inward-rectifier K+ channel Kir2.1. Several studies have shown that Andersen's syndrome mutations lead to a loss of function of the K+ channel activity in vitro. However, ex vivo studies on isolated patient muscle tissue have not been reported. We have performed muscle biopsies of controls and patients presenting ...
Source: AJP: Cell Physiology - October 1, 2009 Category: Cytology Authors: Sacconi, S., Simkin, D., Arrighi, N., Chapon, F., Larroque, M. M., Vicart, S., Sternberg, D., Fontaine, B., Barhanin, J., Desnuelle, C., Bendahhou, S. Tags: MUSCLE CELL BIOLOGY AND CELL MOTILITY Source Type: journals

Cloning, localization, and functional expression of the electrogenic Na+ bicarbonate cotransporter (NBCe1) from zebrafishEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Mutations in the electrogenic Na+/nHCO3– cotransporter (NBCe1, SLC4A4) cause severe proximal renal tubular acidosis, glaucoma, and cataracts in humans, indicating NBCe1 has a critical role in acid-base homeostasis and ocular fluid transport. To better understand the homeostatic roles and protein ontogeny of NBCe1, we have cloned, localized, and downregulated NBCe1 expression in zebrafish, and examined its transport characteristics when expressed in Xenopus oocytes. Zebrafish NBCe1 (zNBCe1) is 80% identical to published mammalian NBCe1 cDNAs. Like other fish NBCe1 clones, zebrafish NBCe1 is most similar to the pancrea...
Source: AJP: Cell Physiology - October 1, 2009 Category: Cytology Authors: Sussman, C. R., Zhao, J., Plata, C., Lu, J., Daly, C., Angle, N., DiPiero, J., Drummond, I. A., Liang, J. O., Boron, W. F., Romero, M. F., Chang, M.-H. Tags: MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS Source Type: journals

Identification of subdomains in NADPH oxidase-4 critical for the oxygen-dependent regulation of TASK-1 K+ channelsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Hypoxic inhibition of K+ current is a critical O2-sensing mechanism. Previously, it was demonstrated that the cooperative action of TASK-1 and NADPH oxidase-4 (NOX4) mediated the O2-sensitive K+ current response. Here we addressed the O2-sensing mechanism of NOX4 in terms of TASK-1 regulation. In TASK-1 and NOX4-coexpressing human embryonic kidney 293 cells, hypoxia (5% O2) decreased the amplitude of TASK-1 current (hypoxia-ITASK-1). To examine whether reactive oxygen species (ROS) mediate the hypoxia-ITASK-1, we treated the cells with carbon monoxide (CO) which is known to reduce ROS generation from the heme-containing NO...
Source: AJP: Cell Physiology - October 1, 2009 Category: Cytology Authors: Park, S. J., Chun, Y.-S., Park, K. S., Kim, S. J., Choi, S.-O., Kim, H.-L., Park, J.-W. Tags: MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS Source Type: journals

Chloride transport in mitochondrion-rich cells of euryhaline tilapia (Oreochromis mossambicus) larvaeEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study provides direct and convincing evidence for Cl– transport by MRCs of SW- and FW-acclimated euryhaline tilapia and the involvement of an apical NCC in Cl– uptake of MRCs of FW-acclimated fish. (Source: AJP: Cell Physiology)
Source: AJP: Cell Physiology - October 1, 2009 Category: Cytology Authors: Horng, J.-L., Hwang, P.-P., Shih, T.-H., Wen, Z.-H., Lin, C.-S., Lin, L.-Y. Tags: MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS Source Type: journals

PKC induces internalization and retention of the EAAC1 glutamate transporter in recycling endosomes of MDCK cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Here we show that stimulation of protein kinase C (PKC) by phorbol 12-myristate 13-acetate (PMA) treatment induces a time-dependent decrease in glutamate transport activity due to relocalization of the excitatory amino acid carrier 1 (EAAC1) glutamate transporter from the apical surface of polarized epithelial Madin-Darby canine kidney (MDCK) cells to intracellular compartments. The PKC-induced internalization of EAAC1 is negatively regulated by the calcineurin inhibitor cyclosporine A and by the expression of a dominant-negative mutant of the endocytic protein dynamin 1, a well-known target of the phosphatase activity of ...
Source: AJP: Cell Physiology - October 1, 2009 Category: Cytology Authors: Padovano, V., Massari, S., Mazzucchelli, S., Pietrini, G. Tags: MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS Source Type: journals

Membrane trauma and Na+ leak from Nav1.6 channelsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
During brain trauma, white matter experiences shear and stretch forces that, without severing axons, nevertheless trigger their secondary degeneration. In central nervous system (CNS) trauma models, voltage-gated sodium channel (Nav) blockers are neuroprotective. This, plus the rapid tetrodotoxin-sensitive Ca2+ overload of stretch-traumatized axons, points to "leaky" Nav channels as a pivotal early lesion in brain trauma. Direct effects of mechanical trauma on neuronal Nav channels have not, however, been tested. Here, we monitor immediate responses of recombinant neuronal Nav channels to stretch, using patch-clamp and Na+...
Source: AJP: Cell Physiology - October 1, 2009 Category: Cytology Authors: Wang, J. A., Lin, W., Morris, T., Banderali, U., Juranka, P. F., Morris, C. E. Tags: MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS Source Type: journals

Focal adhesion kinase modulates activation of NF-{kappa}B by flow in endothelial cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Atherogenesis involves activation of NF-B in endothelial cells by fluid shear stress. Because this pathway involves integrins, we investigated the involvement of focal adhesion kinase (FAK). We found that FAK was not required for flow-stimulated translocation of the p65 NF-B subunit to the nucleus but was essential for phosphorylation of p65 on serine 536 and induction of ICAM-1, an NF-B-dependent gene. NF-B activation by TNF- or hydrogen peroxide was FAK independent. Events upstream of NF-B, including integrin activation, Rac activation, reactive oxygen production, and degradation of IB, were FAK independent. FAK therefor...
Source: AJP: Cell Physiology - October 1, 2009 Category: Cytology Authors: Petzold, T., Orr, A. W., Hahn, C., Jhaveri, K. A., Parsons, J. T., Schwartz, M. A. Tags: VASCULAR BIOLOGY Source Type: journals