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Role for intestinal cyp2e1 in alcohol-induced circadian gene-mediated intestinal hyperpermeability.
Conclusion. Our data support a novel role for intestinal CYP2E1 in alcohol-induced intestinal hyperpermeability via a mechanism involving CYP2E1-dependent induction of oxidative stress and upregulation of circadian clock proteins CLOCK and PER2. PMID: 23660503 [PubMed - as supplied by publisher]
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - May 9, 2013 Category: Physiology Authors: Forsyth CB, Voigt RM, Shaikh M, Tang Y, Cederbaum AI, Turek FW, Keshavarzian A Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Activation of G protein-coupled bile acid receptor, TGR5 induces smooth muscle relaxation via both Epac- and PKA-mediated inhibition of RhoA/Rho kinase pathway.
Abstract The present study characterized the TGR5 expression, and the signaling pathways coupled to this receptor that mediates the relaxation of gastric smooth muscle. TGR5 was detected in gastric muscle cells by RT-PCR and western blotting. Treatment of cells with the TGR5-selective ligand oleanolic acid (OA) activated Gαs, but not Gαq, Gαi1, Gαi2, or Gαi3, and increased cAMP levels. OA did not elicit contraction, but caused relaxation of carbachol-induced contraction of gastric muscle cells from wild type mice, but not tgr5-/- mice. OA, but not a selective Epac ligand (8-pCPT-2'-O-Me-cAMP), caused phosphor...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - December 28, 2012 Category: Physiology Authors: Rajagopal S, Kumar DP, Mahavadi S, Bhattacharya S, Zhou R, Corvera C, Bunnett NW, Grider JR, Murthy KS Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Epidermal Growth Factor Receptor Expression and Signaling Is Essential in Glutamine's Cytoprotective Mechanism in Heat-Stressed Intestinal Epithelial-6 Cells.
Abstract Epidermal growth factor receptor (EGFR) expression and signaling can induce cellular protection after intestinal inflammation. L-glutamine (GLN) is known to prevent apoptosis after intestinal injury by activating mitogen-activated protein kinase and phosphatidylinositol 3-kinase (PI3-K)/Akt pathways. However, it is currently unknown what role EGFR expression and signaling play in GLN-mediated cellular protection in intestinal epithelial-6 (IEC-6) cells after heat stress (HS). To address the role of EGFR in GLN's protection, IEC-6 cells were treated with GLN in the presence or absence of EGFR siRNA, EGFR t...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - December 28, 2012 Category: Physiology Authors: Niederlechner S, Baird C, Petrie B, Wischmeyer E, Wischmeyer PE Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

THE IGF2 mRNA BINDING PROTEIN p62 IN HEPATOCELLULAR CARCINOMA: ANTI-APOPTOTIC ACTION IS INDEPENDENT OF IGF2/PI3-K SIGNALING.
Conclusions: Our data demonstrate that p62 exerts IGF2-independent anti-apoptotic action, which is facilitated via phosphorylation of ERK1/2. Furthermore, p62 might serve as a new prognostic marker in HCC. PMID: 23257922 [PubMed - as supplied by publisher]
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - December 20, 2012 Category: Physiology Authors: Kessler SM, Pokorny J, Zimmer V, Laggai S, Lammert F, Bohle RM, Kiemer AK Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Expression of bile acid receptor TGR5 in gastric adenocarcinoma.
In this study we determined the expression of TGR5 in gastric adenocarcinoma and examined the role of TGR5 in cell proliferation. Strong TGR5 staining was present in 12% of cases of intestinal metaplasia but in no cases of normal gastric epithelium (p<0.01). Moderate to strong TGR5 membranous and cytoplasmic staining was present in 52% of the intestinal but in only 25% of the diffuse subtype of adenocarcinomas (p<0.001). Kaplan-Meier univariate survival analysis revealed that moderate to strong TGR5 staining was associated with decreased patient survival (p<0.05). Treatment with taurodeoxycholic acid (TDCA, a bile...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - December 13, 2012 Category: Physiology Authors: Cao W, Tian W, Hong J, Li D, Tavares R, Noble L, Moss SF, Resnick MB Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Sensing of amino acids by the gut-expressed taste receptor, T1R1-T1R3, stimulates CCK secretion.
Abstract Cholecystokinin (CCK) is secreted by endocrine cells of the proximal intestine in response to dietary components, including amino acids. CCK plays a variety of roles in digestive processes, including inhibition of food intake consistent with a role in satiety. In the lingual epithelium, the sensing of a broad spectrum of L-amino acids is accomplished by the T1R1-T1R3 heteromeric amino acid (umami) taste receptor. T1R1 and T1R3 subunits are also expressed in the intestine. A defining characteristic of umami sensing by T1R1-T1R3 is its potentiation by inosine or guanosine 5'-monophosphates (IMP/GMP). Furthe...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - November 29, 2012 Category: Physiology Authors: Daly K, Al-Rammahi M, Moran AW, Marcello M, Ninomiya Y, Shirazi-Beechey SP Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Keratinocyte Growth Factor-2 Stimulates P-glycoprotein Expression and Function in Intestinal Epithelial Cells.
In conclusion, our findings define the post-translational and transcriptional mechanisms underlying stimulation of Pgp function and expression by KGF2 that may contribute to the beneficial effects of KGF2 in intestinal inflammatory disorders. PMID: 23328208 [PubMed - as supplied by publisher]
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - January 17, 2013 Category: Physiology Authors: Saksena S, Priyamvada S, Kumar A, Akhtar M, Soni V, Anbazhagan AN, Alakkam A, Alrefai WA, Dudeja PK, Gill RK Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Chymase mediated intestinal epithelial permeability is regulated by protease activating receptor (PAR)-2/ matrix metalloproteinase (MMP)-2-dependent mechanism.
Abstract Mast cells regulate intestinal barrier function during disease and homeostasis. Homeostatic regulation in vivo is through secretion of the mast cell-specific serine protease chymase. In the present study, we employ in vitro model systems to delineate the molecular pathways involved in chymase-mediated intestinal epithelial barrier dysfunction. Chymase stimulation of intestinal epithelial cell monolayers (Caco2bbe) induced a significant reduction in transepithelial resistance indicating decreased intestinal epithelial barrier function. The chymase-induced intestinal epithelial barrier dysfunction was chara...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - January 10, 2013 Category: Physiology Authors: Groschwitz KR, Wu D, Osterfeld H, Ahrens R, Hogan SP Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

BMP2 Inhibits TGF-β-Induced Pancreatic Stellate Cell Activation and Extracellular Matrix Formation.
Abstract Activation of pancreatic stellate cells (PSCs) by transforming growth factor (TGF)-β is the key step in the development of pancreatic fibrosis, a common pathologic feature of chronic pancreatitis (CP). Bone morphogenetic proteins (BMPs), members of TGF-β superfamily, have anti-fibrogenic functions, in contrast to TGF-β, in the kidney, lung and liver. However, it is not known whether BMPs have anti-fibrogenic role in the pancreas. The current study was designed to investigate the potential anti-fibrogenic role of BMPs in the pancreas using an in vivo chronic pancreatitis model and an in vitro pancreatic...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - February 21, 2013 Category: Physiology Authors: Gao X, Cao Y, Yang W, Duan C, Aronson JF, Rastellini C, Chao C, Hellmich MR, Ko TC Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Glyoxalate reductase/hydroxypyruvate reductase interacts with the sodium-dependent vitamin C transporter-1 to regulate cellular vitamin C homeostasis.
Abstract The human sodium-dependent vitamin C transporter 1 (hSVCT1) contributes to cellular uptake of ascorbic acid (AA). While different aspects of hSVCT1 cell biology have been extensively studied, nothing is currently known about the broader hSVCT1 interactome that modulates its role in cellular physiology. Here, we identify the enzyme human glyoxalate reductase/hydroxypyruvate reductase (hGR/HPR) as an hSVCT1 associated protein by yeast two-hybrid (Y2H) screening of a human liver cDNA library. The interaction between hSVCT1 and hGR/HPR was further confirmed by in vitro GST-pull-down assay, in vivo co-immunopr...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - April 18, 2013 Category: Physiology Authors: Subramanian VS, Nabokina SM, Patton JR, Marchant JS, Moradi H, Said HM Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Emerging neuropeptide targets in inflammation - NPY and VIP.
Abstract The enteric nervous system (ENS) referred to as the 'second brain' comprises a vast number of neurons that form an elegant network throughout the gastrointestinal (GI) tract. Neuropeptides produced by the ENS play a crucial role in the regulation of inflammatory processes via cross talk with the enteric immune system. In addition, neuropeptides have paracrine effects on epithelial secretion, thus regulating epithelial barrier functions and thereby susceptibility to inflammation. Ultimately the inflammatory response damages the enteric neurons themselves resulting in deregulations in circuitry and gut moti...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - March 28, 2013 Category: Physiology Authors: Chandrasekharan B, Nezami BG, Srinivasan S Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Increased PDE5 Activity and Decreased Rho Kinase and PKC Activities in Colonic Muscle from Caveolin-1-/- Mice Impairs the Peristaltic Reflex and Propulsion.
Abstract Caveolae are specialized regions of the plasma membrane that concentrate receptors and associated signaling molecules critical in regulation of cellular response to transmitters and hormones. We have determined the effects of caveolin-1 (Cav-1) deletion, caveolin-1 siRNA, and caveolar disruption in mice on the signaling pathways that mediate contraction and relaxation in colonic smooth muscle, and on the components of the peristaltic reflex in isolated tissue and propulsion in intact colonic segments. In Cav-1(-/-) mice, both relaxation and contraction were decreased in smooth muscle cells and muscle stri...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - October 24, 2013 Category: Physiology Authors: Mahavadi S, Bhattacharya S, Kumar DP, Clay C, Ross GR, Akbarali HI, Grider JR, Murthy KS Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Functional Involvement of RFVT3/SLC52A3 in Intestinal Riboflavin Absorption.
In this study, we investigated the functional involvement of RFVT3 in riboflavin absorption using intestinal epithelial T84 cells and mouse small intestine. T84 cells expressed RFVT3 and conserved unidirectional riboflavin transport corresponding to intestinal absorption. Apical [(3)H]riboflavin uptake was pH-dependent in T84 cells. This uptake was not affected by Na(+) depletion at apical pH 6.0, although it was significantly decreased at apical pH 7.4. The [(3)H]riboflavin uptake from the apical side of T84 cells was prominently inhibited by the RFVT3 selective inhibitor, methylene blue, and significantly decreased by tr...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - November 21, 2013 Category: Physiology Authors: Yoshimatsu H, Yonezawa A, Yao Y, Sugano K, Nakagawa S, Omura T, Matsubara K Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Inhibitory Signaling by CB1 Receptors in Smooth Muscle Mediated by GRK5/beta-Arrestin Activation of ERK1/2 and Src.
We examined whether CB1 receptors in smooth muscle conform to the signaling pattern observed with other Gi-coupled receptors that stimulate contraction via two Gβγ-dependent pathways (PLC-β3 and PI 3-kinase/integrin-linked kinase). Here we show that the anticipated Gβγ-dependent signaling was abrogated. Except for inhibition of adenylyl cyclase via Gαi, signaling resulted from Gβγ-independent phosphorylation of CB1 receptors by GRK5, recruitment of β-arrestin1/2, and activation of ERK1/2 and Src kinase. Neither uncoupling of CB1 receptors from Gi by PTx or Gi minigene, nor expression of a Gβγ-scavenging peptide ...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - January 9, 2014 Category: Physiology Authors: Mahavadi S, Sriwai W, Huang J, Grider JR, Murthy KS Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Helicobacter pylori-induced post-transcriptional regulation of H,K-ATPase α subunit gene expression by miRNA.
Abstract Acute H. pylori infection of gastric epithelial cells induces CagA oncoprotein- and peptidoglycan (SLT)-dependent mobilization of NF-κB p50 homodimers that bind to H,K-ATPase α subunit (HKα) promoter and repress HKα gene transcription. This process may facilitate gastric H. pylori colonization by induction of transient hypochlorhydria. We hypothesized that H. pylori also regulates HKα expression post-transcriptionally by miRNA interaction with HKα mRNA. In silico analysis of HKα 3' untranslated region (UTR) identified miR-1289 as a highly-conserved putative HKα-regulatory miRNA. H. pylori infectio...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - February 6, 2014 Category: Physiology Authors: Zhang YM, Noto JM, Hammond CE, Barth JL, Argraves WS, Backert S, Peek RM, Smolka AJ Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

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