PubMed Central (PMC3 - NLM DTD)
(2,525,429 recursos)
Archive of life sciences journal literature at the U.S. National Institutes of Health (NIH), developed and managed by NIH's National Center for Biotechnology Information (NCBI) in the National Library of Medicine (NLM).
American Journal of Physiology - Gastrointestinal and Liver Physiology
Mostrando recursos 121 - 140 de 592
121.
Abdominal surgery inhibits circulating acyl ghrelin and ghrelin-O-acyltransferase levels in rats: role of the somatostatin receptor subtype 2 - Stengel, Andreas; Goebel-Stengel, Miriam; Wang, Lixin; Shaikh, Almaas; Lambrecht, Nils W. G.; Rivier, Jean; Taché, Yvette
Clinical studies are evaluating the efficacy of synthetic ghrelin agonists in postoperative ileus management. However, the control of ghrelin secretion under conditions of postoperative gastric ileus is largely unknown. Peripheral somatostatin inhibits ghrelin secretion in animals and humans. We investigated the time course of ghrelin changes postsurgery in fasted rats and whether somatostatin receptor subtype 2 (sst2) signaling is involved. Abdominal surgery (laparotomy and 1-min cecal palpation) induced a rapid and long-lasting decrease in plasma acyl ghrelin levels as shown by the 64, 67, and 59% reduction at 0.5, 2, and 5 h postsurgery, respectively, compared with sham (anesthesia alone...
122.
TNF transactivation of EGFR stimulates cytoprotective COX-2 expression in gastrointestinal epithelial cells - Hobbs, Stuart S.; Goettel, Jeremy A.; Liang, Dongchun; Yan, Fang; Edelblum, Karen L.; Frey, Mark R.; Mullane, Matthew T.; Polk, D. Brent
TNF and epidermal growth factor (EGF) are well-known stimuli of cyclooxygenase (COX)-2 expression, and TNF stimulates transactivation of EGF receptor (EGFR) signaling to promote survival in colon epithelial cells. We hypothesized that COX-2 induction and cell survival signaling downstream of TNF are mediated by EGFR transactivation. TNF treatment was more cytotoxic to COX-2−/− mouse colon epithelial (MCE) cells than wild-type (WT) young adult mouse colon (YAMC) epithelial cells or COX-1−/− cells. TNF also induced COX-2 protein and mRNA expression in YAMC cells, but blockade of EGFR kinase activity or expression inhibited COX-2 upregulation. TNF-induced COX-2 expression was reduced and absent...
123.
B-vitamin deficiency is protective against DSS-induced colitis in mice - Benight, Nancy M.; Stoll, Barbara; Chacko, Shaji; da Silva, Vanessa R.; Marini, Juan C.; Gregory, Jesse F.; Stabler, Sally P.; Burrin, Douglas G.
Vitamin deficiencies are common in patients with inflammatory bowel disease (IBD). Homocysteine (Hcys) is a thrombogenic amino acid produced from methionine (Met), and its increase in patients with IBD indicates a disruption of Met metabolism; however, the role of Hcys and Met metabolism in IBD is not well understood. We hypothesized that disrupted Met metabolism from a B-vitamin-deficient diet would exacerbate experimental colitis. Mice were fed a B6-B12-deficient or control diet for 2 wk and then treated with dextran sodium sulfate (DSS) to induce colitis. We monitored disease activity during DSS treatment and collected plasma and tissue for analysis of...
124.
Deoxycholic acid causes DNA damage while inducing apoptotic resistance through NF-κB activation in benign Barrett's epithelial cells - Huo, Xiaofang; Juergens, Stefanie; Zhang, Xi; Rezaei, Davood; Yu, Chunhua; Strauch, Eric D.; Wang, Jian-Ying; Cheng, Edaire; Meyer, Frank; Wang, David H.; Zhang, Qiuyang; Spechler, Stuart J.; Souza, Rhonda F.
Gastroesophageal reflux is associated with adenocarcinoma in Barrett's esophagus, but the incidence of this tumor is rising, despite widespread use of acid-suppressing medications. This suggests that refluxed material other than acid might contribute to carcinogenesis. We looked for potentially carcinogenetic effects of two bile acids, deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA), on Barrett's epithelial cells in vitro and in vivo. We exposed Barrett's (BAR-T) cells to DCA or UDCA and studied the generation of reactive oxygen/nitrogen species (ROS/RNS); expression of phosphorylated H2AX (a marker of DNA damage), phosphorylated IkBα, and phosphorylated p65 (activated NF-κB pathway proteins); and apoptosis. During...
125.
Knockout of the neurokinin-1 receptor reduces cholangiocyte proliferation in bile duct-ligated mice - Glaser, Shannon; Gaudio, Eugenio; Renzi, Anastasia; Mancinelli, Romina; Ueno, Yoshiyuki; Venter, Julie; White, Mellanie; Kopriva, Shelley; Chiasson, Valorie; DeMorrow, Sharon; Francis, Heather; Meng, Fanyin; Marzioni, Marco; Franchitto, Antonio; Alvaro, Domenico; Supowit, Scott; DiPette, Donald J.; Onori, Paolo; Alpini, Gianfranco
In bile duct-ligated (BDL) rats, cholangiocyte proliferation is regulated by neuroendocrine factors such as α-calcitonin gene-related peptide (α-CGRP). There is no evidence that the sensory neuropeptide substance P (SP) regulates cholangiocyte hyperplasia. Wild-type (WT, +/+) and NK-1 receptor (NK-1R) knockout (NK-1R−/−) mice underwent sham or BDL for 1 wk. Then we evaluated 1) NK-1R expression, transaminases, and bilirubin serum levels; 2) necrosis, hepatocyte apoptosis and steatosis, and the number of cholangiocytes positive by CK-19 and terminal deoxynucleotidyl transferase biotin-dUTP nick-end labeling in liver sections; 3) mRNA expression for collagen 1α and α-smooth muscle (α-SMA) actin in total liver samples; and...
126.
TNF-α converting enzyme-mediated ErbB4 transactivation by TNF promotes colonic epithelial cell survival - Hilliard, Valda C.; Frey, Mark R.; Dempsey, Peter J.; Peek, Richard M.; Polk, D. Brent
Disruption of intestinal epithelial homeostasis, including enhanced apoptosis, is a hallmark of inflammatory bowel disease (IBD). We have recently shown that tumor necrosis factor (TNF) increases the kinase activity of ErbB4, a member of the epidermal growth factor receptor family that is elevated in mucosa of IBD patients and that promotes colon epithelial cell survival. In this study, we tested the hypothesis that TNF transactivates ErbB4 through TNF-α converting enzyme (TACE)-mediated ligand release and that this transactivation is necessary to protect colonic epithelial cells from cytokine-induced apoptosis. Using neutralizing antibodies, we show that heparin-binding EGF-like growth factor (HB-EGF) is required...
127.
Immunocytochemical evidence for PDBu-induced activation of RhoA/ROCK in human internal anal sphincter smooth muscle cells - Singh, Jagmohan; Maxwell, Pinckney J.; Rattan, Satish
Studies were performed to determine the unknown status of PKC and RhoA/ROCK in the phorbol 12,13-dibutyrate (PDBu)-stimulated state in the human internal anal sphincter (IAS) smooth muscle cells (SMCs). We determined the effects of PDBu (10−7 M), the PKC activator, on PKCα and RhoA and ROCK II translocation in the human IAS SMCs. We used immunocytochemistry and fluorescence microcopy in the basal state, following PDBu, and before and after PKC inhibitor calphostin C (10−6 M), cell-permeable RhoA inhibitor C3 exoenzyme (2.5 μg/ml), and ROCK inhibitor Y 27632 (10−6 M). We also determined changes in the SMC lengths via computerized digital...
128.
Specific epidermal growth factor receptor autophosphorylation sites promote mouse colon epithelial cell chemotaxis and restitution - Yamaoka, Toshimitsu; Frey, Mark R.; Dise, Rebecca S.; Bernard, Jessica K.; Polk, D. Brent
Upon ligand binding, epidermal growth factor (EGF) receptor (R) autophosphorylates on COOH-terminal tyrosines, generating docking sites for signaling partners that stimulate proliferation, restitution, and chemotaxis. Specificity for individual EGFR tyrosines in cellular responses has been hypothesized but not well documented. Here we tested the requirement for particular tyrosines, and associated downstream pathways, in mouse colon epithelial cell chemotactic migration. We compared these requirements to those for the phenotypically distinct restitution (wound healing) migration. Wild-type, Y992/1173F, Y1045F, Y1068F, and Y1086F EGFR constructs were expressed in EGFR−/− cells; EGF-induced chemotaxis or restitution were determined by Boyden chamber or modified scratch wound assay,...
129.
Glutathione peroxidase-3 produced by the kidney binds to a population of basement membranes in the gastrointestinal tract and in other tissues - Burk, Raymond F.; Olson, Gary E.; Winfrey, Virginia P.; Hill, Kristina E.; Yin, Dengping
Glutathione peroxidase-3 (Gpx3), the extracellular glutathione peroxidase synthesized largely in the kidney, binds to basement membranes of renal cortical epithelial cells. The present study assessed extrarenal expression of Gpx3 using RT-PCR and presence of Gpx3 protein using immunocytochemistry. Gpx3 expression was higher in kidney and epididymis than in other tissues. Gpx3 bound to basement membranes of epithelial cells in the gastrointestinal tract, the efferent ducts connecting the seminiferous tubules with the epididymis, the bronchi, and type II pneumocytes. It was not detected on the basement membrane of type I pneumocytes. Gpx3 was also present in the lumen of the epididymis....
130.
ERK is involved in EGF-mediated protection of tight junctions, but not adherens junctions, in acetaldehyde-treated Caco-2 cell monolayers - Samak, G.; Aggarwal, S.; Rao, R. K.
The role of mitogen-activated protein kinases (MAPK) in the mechanism of EGF-mediated prevention of acetaldehyde-induced tight junction disruption was evaluated in Caco-2 cell monolayers. Pretreatment of cell monolayers with EGF attenuated acetaldehyde-induced decrease in resistance and increase in inulin permeability and redistribution of occludin, zona occludens-1 (ZO-1), E-cadherin, and β-catenin from the intercellular junctions. EGF rapidly increased the levels of phospho-ERK1/2, phospho-p38 MAPK, and phospho-JNK1. Pretreatment of cell monolayers with U-0126 (inhibitor of ERK activation), but not SB-202190 and SP-600125 (p38 MAPK and JNK inhibitors), significantly attenuated EGF-mediated prevention of acetaldehyde-induced changes in resistance, inulin permeability, and redistribution of occludin...
131.
SREBP2 mediates the modulation of intestinal NPC1L1 expression by curcumin - Kumar, Pradeep; Malhotra, Pooja; Ma, Ke; Singla, Amika; Hedroug, Omar; Saksena, Seema; Dudeja, Pradeep K.; Gill, Ravinder K.; Alrefai, Waddah A.
Curcumin, the major phenolic compound in the spice turmeric, exhibits numerous biological effects, including lowering plasma cholesterol and preventing diet-induced hypercholesterolemia. The mechanisms underlying the hypocholesterolemic effect of curcumin are not fully understood. In this regard, intestinal Niemann-Pick C1-like 1 (NPC1L1) cholesterol transporter, the molecular target of intestinal cholesterol absorption inhibitor ezetimibe, plays an essential role in the maintenance of cholesterol homeostasis. The current studies were designed to investigate the effect of curcumin on NPC1L1 function, expression, and promoter activity in intestinal Caco-2 monolayers. NPC1L1 function was evaluated by the measurement of ezetimibe-sensitive [3H]cholesterol esterification. Relative abundance of NPC1L1 mRNA...
132.
Heterogeneous accumulation of fluorescent bile acids in primary rat hepatocytes does not correlate with their homogenous expression of ntcp - Murray, John W.; Thosani, Amar J.; Wang, Pijun; Wolkoff, Allan W.
Sodium taurocholate-cotransporting polypeptide (ntcp) is considered to be a major determinant of bile acid uptake into hepatocytes. However, the regulation of ntcp and the degree that it participates in the accumulation of specific substrates are not well understood. We utilized fluorescent bile acid derivatives and direct quantitation of fluorescent microscopy images to examine the regulation of ntcp and its role in the cell-to-cell variability of fluorescent bile acid accumulation. Primary-cultured rat hepatocytes rapidly accumulated the fluorescent bile acids, chenodeoxycholylglycylamidofluorescein (CDCGamF), 7-β- nitrobenzoxadiazole 3-α hydroxy 5-β cholan-24-oic acid (NBD-CA), and cholyl-glycylamido-fluorescein (CGamF). However, in stably transfected HeLa cells, ntcp preferred CDCGamF,...
133.
Role of cysteine residues in cell surface expression of the human riboflavin transporter-2 (hRFT2) in intestinal epithelial cells - Subramanian, Veedamali S.; Rapp, Laramie; Marchant, Jonathan S.; Said, Hamid M.
The water-soluble vitamin B2 (riboflavin, RF) is an essential micronutrient for normal cell function and survival. Recent studies have identified a role for the human riboflavin transporter-2 (hRFT2) in normal intestinal RF absorption. However, little is known about the cell biology of this transporter and specifically about the molecular determinant(s) that dictate its cell surface expression in human intestinal epithelial cells. Here we show that the full-length hRFT2 protein fused to green fluorescent protein (GFP) (GFP-hRFT2) is expressed exclusively at the apical membrane domain of Caco-2 cells. COOH-terminal sequence was essential in dictating cell surface expression with a specific role...
134.
Toll-like receptor 3 signaling enables human esophageal epithelial cells to sense endogenous danger signals released by necrotic cells - Lim, Diana M.; Wang, Mei-Lun
The mechanisms by which gastroesophageal reflux disease esophagitis develops are controversial. Although many support the notion that caustic injury leads to reflux esophagitis, others have proposed that reflux esophagitis is caused by esophageal epithelial cytokine-mediated inflammation. We previously demonstrated that Toll-like receptor 3 (TLR3) is highly expressed and functional in the nontransformed human esophageal epithelial cell line EPC2-hTERT. In addition to activation by viral double-stranded RNA, TLR3 can be activated by endogenous mRNA released by necrotic cells. In the present study, we investigated the role of esophageal epithelial TLR3 to sense danger signals released by necrotic esophageal epithelial cells in...
135.
Dietary fiber enhances TGF-β signaling and growth inhibition in the gut - Cao, Yanna; Gao, Xuxia; Zhang, Weili; Zhang, Guohua; Nguyen, Anthony K.; Liu, Xianghua; Jimenez, Fernando; Cox, Charles S.; Townsend, Courtney M.; Ko, Tien C.
Dietary fiber intake links to decreased risk of colorectal cancers. The underlying mechanisms remain unclear. Recently, we found that butyrate, a short-chain fatty acid produced in gut by bacterial fermentation of dietary fiber, enhances TGF-β signaling in rat intestinal epithelial cells (RIE-1). Furthermore, TGF-β represses inhibitors of differentiation (Ids), leading to apoptosis. We hypothesized that dietary fiber enhances TGF-β's growth inhibitory effects on gut epithelium via inhibition of Id2. In this study, Balb/c and DBA/2N mice were fed with a regular rodent chow or supplemented with a dietary fiber (20% pectin) and Smad3 level in gut epithelium was measured. In...
136.
Polyamines mediate glutamine-dependent induction of the intestinal epithelial heat shock response - Iwashita, Yuji; Sakiyama, Toshio; Musch, Mark W.; Ropeleski, Mark J.; Tsubouchi, Hirohito; Chang, Eugene B.
Heat shock proteins (Hsps) are highly conserved proteins that play a role in cytoprotection and maintaining intestinal homeostasis. Glutamine is essential for the optimal induction of intestinal epithelial Hsp expression, but its mechanisms of action are incompletely understood. Glutamine is a substrate for polyamine synthesis and stimulates the activity of ornithine decarboxylase (ODC), a key enzyme for polyamine synthesis, in intestinal epithelial cells. Thus we investigated whether polyamines (putrescine, spermidine, or spermine) and their precursor ornithine mediate the induction of Hsp expression in IEC-18 rat intestinal epithelial cells. As previously observed, glutamine was required for heat stress induction of Hsp70...
137.
Hypoxia-inducible factor-2α and iron absorptive gene expression in Belgrade rat intestine - Yeh, Kwo-yih; Yeh, Mary; Polk, Paula; Glass, Jonathan
The divalent metal transporter (DMT1, Slc11a2) is an important molecule for intestinal iron absorption. In the Belgrade (b/b) rat, the DMT1 G185R mutation markedly decreases intestinal iron absorption. We used b/b rats as a model to examine the genes that could be compensatory for decreased iron absorption. When tissue hypoxia was assayed by detecting pimonidazole HCl adducts, the b/b liver and intestine exhibited more adducts than the +/+ rats, suggesting that hypoxia might signal altered gene expression. Total RNA in the crypt-villus bottom (C-pole) and villus top (V-pole) of +/+, b/b, and iron-fed b/b rats was isolated for gene array...
138.
Colitis decreases mechanosensitive K2P channel expression and function in mouse colon sensory neurons - La, Jun-Ho; Gebhart, G. F.
TREK-1, TREK-2 and TRAAK are mechanosensitive two-pore domain K+ (K2P) channels thought to be involved in the attenuation of mechanotransduction. Because colon inflammation is associated with colon mechanohypersensitivity, we hypothesized that the role of these channels in colon sensory (dorsal root ganglion, DRG) neurons would be reduced by colon inflammation. Accordingly, we studied the functional expression of mechanosensitive K2P channels in colon sensory neurons in both thoracolumbar (TL) and lumbosacral (LS) DRG that represent the splanchnic and pelvic nerve innervations of the colon, respectively. In colon DRG neurons identified by retrograde tracer previously injected into the colon wall, 62% of...
139.
Hepatic stellate cells require a stiff environment for myofibroblastic differentiation - Olsen, Abby L.; Bloomer, Steven A.; Chan, Erick P.; Gaça, Marianna D. A.; Georges, Penelope C.; Sackey, Bridget; Uemura, Masayuki; Janmey, Paul A.; Wells, Rebecca G.
The myofibroblastic differentiation of hepatic stellate cells (HSC) is a critical event in liver fibrosis and is part of the final common pathway to cirrhosis in chronic liver disease from all causes. The molecular mechanisms driving HSC differentiation are not fully understood. Because macroscopic tissue stiffening is a feature of fibrotic disease, we hypothesized that mechanical properties of the underlying matrix are a principal determinant of HSC activation. Primary rat HSC were cultured on inert polyacrylamide supports of variable but precisely defined shear modulus (stiffness) coated with different extracellular matrix proteins or poly-l-lysine. HSC differentiation was determined by cell morphology,...
140.
Effect of nifedipine on anorectal sensorimotor functions in health and fecal incontinence - Bharucha, Adil E.; Edge, Jessica; Zinsmeister, Alan R.
The mechanisms of increased rectal stiffness in women with fecal incontinence (FI) and rectal urgency are not understood. Our hypothesis was that distention-induced activation of mechanosensitive L-type calcium channels in smooth muscle contributes to increased rectal stiffness in FI. Anal pressures, rectal distensibility (compliance, capacity, and contractile response to sinusoidal oscillation), and rectal sensation were assessed before and after oral nifedipine (30 + 10 mg) or placebo in 16 women with FI and 16 asymptomatic women. At baseline, FI patients had a lower anal pressure increment during squeeze (health, 66.9 ± 7.6: FI, 28.6 ± 5.9, mean ± SE, P...
121.
