Nitric oxide regulates energy metabolism and Bcl-2 expression in intestinal epithelial cells

1998 ◽  
Vol 274 (5) ◽  
pp. G797-G801 ◽  
Author(s):  
Manabu Nishikawa ◽  
Kenta Takeda ◽  
Eisuke F. Sato ◽  
Tetso Kuroki ◽  
Masayasu Inoue
Keyword(s):  
Nitric Oxide ◽  
Epithelial Cells ◽  
Prolonged Exposure ◽  
Intestinal Epithelial Cells ◽  
Enteric Bacteria ◽  
Intestinal Lumen ◽  
Intestinal Epithelial ◽  
Mucosal Cells ◽  
Respiration Of Mitochondria ◽  
Induced Changes

Nitric oxide (NO) inhibits the respiration of mitochondria and enteric bacteria, particularly under low O2concentration, and induces apoptosis of various types of cells. To gain insight into the molecular role of NO in the intestine, we examined its effects on the respiration, Ca2+status, and expression of Bcl-2 in cultured intestinal epithelial cells (IEC-6). NO reversibly inhibited the respiration of IEC-6 cells, especially under physiologically low O2concentration. Although NO elevated cytosolic Ca2+as determined by the fura 2 method, the cells were fairly resistant to NO. Kinetic analysis revealed that prolonged exposure to NO elevated the levels of Bcl-2 and suppressed the NO-induced changes in Ca2+status of the cells. Because Bcl-2 possesses antiapoptotic function, toxic NO effects might appear minimally in enterocytes enriched with Bcl-2. Thus NO might effectively exhibit its antibacterial action in anaerobic intestinal lumen without inducing apoptosis of Bcl-2-enriched mucosal cells.

Epidermal growth factor and interleukin-1β synergistically stimulate the production of nitric oxide in rat intestinal epithelial cells

2004 ◽  
Vol 287 (6) ◽  
pp. G1188-G1193 ◽  
Author(s):  
Katsuhiko Kitagawa ◽  
Yoshinori Hamada ◽  
Yasunori Kato ◽  
Koji Nakai ◽  
Mikio Nishizawa ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Pi3 Kinase ◽  
Intestinal Epithelial ◽  
Simultaneous Addition ◽  
Epidermal Growth ◽  
Inos Induction

Epidermal growth factor (EGF) is one of the trophic factors for intestinal adaptation after small bowel transplantation (SBT). A recent report indicates that nitric oxide (NO) has cytoprotective effects on bacterial translocation (BT) after SBT. We hypothesized that EGF stimulates the expression of the inducible NO synthase (iNOS) gene in the graft after SBT, followed by increased production of NO, resulting in the decrease of BT. Intestinal epithelial cells (IEC)-6 were treated with EGF and/or IL-1β in the presence and absence of phosphatidylinositol 3-kinase (PI3-kinase) and EGF receptor kinase inhibitors (LY-294002 and tyrphostin A25). The induction of NO production and iNOS and its signal molecules, including the inhibitory protein of NF-κB (IκB), NF-κB, and Akt, were analyzed. IL-1β stimulated the degradation of IκB and the activation of NF-κB but had no effect on iNOS induction. EGF, which had no effect on the NF-κB activation and iNOS induction, stimulated the upregulation of type 1 IL-1 receptor (IL-1R1) through PI3-kinase/Akt. Simultaneous addition of EGF and IL-1β stimulated synergistically the induction of iNOS, leading to the increased production of NO. Our results indicate that EGF and IL-1β stimulate two essential signals for iNOS induction in IEC-6 cells: the upregulation of IL-1R1 through PI3-kinase/Akt and the activation of NF-κB through IκB kinase, respectively. Simultaneous addition of EGF and IL-1β can enhance the production of NO, which may contribute to the cytoprotective effect of EGF against intestinal injury.

scholarly journals SALMONELLA INDUCES PRODUCTION OF NITRIC OXIDE IN INTESTINAL EPITHELIAL CELLS IN VITRO

1997 ◽  
Vol 75 ◽  
pp. 91
Author(s):  
M. Saarinen ◽  
P. Laitio ◽  
M. Salmi ◽  
Q. He ◽  
D.T.Y. Yu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial

Protease-activated receptor-1 stimulates Ca2+-dependent Cl−secretion in human intestinal epithelial cells

2001 ◽  
Vol 281 (2) ◽  
pp. G323-G332 ◽  
Author(s):  
M. C. Buresi ◽  
E. Schleihauf ◽  
N. Vergnolle ◽  
A. Buret ◽  
J. L. Wallace ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Short Circuit ◽  
Intestinal Lumen ◽  
Epithelial Cell Line ◽  
Intracellular Camp ◽  
Intestinal Epithelial ◽  
Rt Pcr ◽  
Human Intestinal Epithelial Cells ◽  
Protease Activated Receptor 1

The thrombin receptor, protease-activated receptor-1 (PAR-1), has wide tissue distribution and is involved in many physiological functions. Because thrombin is in the intestinal lumen and mucosa during inflammation, we sought to determine PAR-1 expression and function in human intestinal epithelial cells. RT-PCR showed PAR-1 mRNA expression in SCBN cells, a nontransformed duodenal epithelial cell line. Confluent SCBN monolayers mounted in Ussing chambers responded to PAR-1 activation with a Cl−-dependent increase in short-circuit current. The secretory effect was blocked by BaCl2and the Ca2+-ATPase inhibitor thapsigargin, but not by the L-type Ca2+channel blocker verapamil or DIDS, the nonselective inhibitor of Ca2+-dependent Cl−transport. Responses to thrombin and PAR-1-activating peptides exhibited auto- and crossdesensitization. Fura 2-loaded SCBN cells had increased fluorescence after PAR-1 activation, indicating increased intracellular Ca2+. RT-PCR showed that SCBN cells expressed mRNA for the cystic fibrosis transmembrane conductance regulator (CFTR) and hypotonicity-activated Cl−channel-2 but not for the Ca2+-dependent Cl−channel-1. PAR-1 activation failed to increase intracellular cAMP, suggesting that the CFTR channel is not involved in the Cl−secretory response. Our data demonstrate that PAR-1 is expressed on human intestinal epithelial cells and regulates a novel Ca2+-dependent Cl−secretory pathway. This may be of clinical significance in inflammatory intestinal diseases with elevated thrombin levels.

scholarly journals Dietary Glucose Increases Glucose Absorption and Lipid Deposition via SGLT1/2 Signaling and Acetylated ChREBP in the Intestine and Isolated Intestinal Epithelial Cells of Yellow Catfish

2020 ◽  
Vol 150 (7) ◽  
pp. 1790-1798 ◽  
Author(s):  
Tao Zhao ◽  
Shui-Bo Yang ◽  
Guang-Hui Chen ◽  
Yi-Huan Xu ◽  
Yi-Chuang Xu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lipid Metabolism ◽  
Epithelial Cells ◽  
Fatty Acid Synthase ◽  
Intestinal Epithelial Cells ◽  
Glucose Absorption ◽  
Lipid Deposition ◽  
Intestinal Epithelial ◽  
Yellow Catfish ◽  
Induced Changes

ABSTRACT Background Dietary carbohydrate affects intestinal glucose absorption and lipid deposition, but the underlying mechanisms are unknown. Objectives We used yellow catfish and their isolated intestinal epithelial cells (IECs) to test the hypothesis that sodium/glucose cotransporters (SGLTs) 1/2 and acetylated carbohydrate response element binding protein (ChREBP) mediated glucose-induced changes in glucose absorption and lipid metabolism. Methods Yellow catfish (mean ± SEM weight: 4.68 ± 0.02 g, 3 mo old, mixed sex) were fed diets containing 250 g carbohydrates/kg from glucose (G, control), corn starch (CS), sucrose (S), potato starch (PS), or dextrin (D) for 10 wk. IECs were isolated from different yellow catfish and incubated for 24 h in a control or glucose (15 mM) solution with or without a 2-h pretreatment with an inhibitor [sotagliflozin (LX-4211) or tubastatin A (TBSA)]. Human embryonic kidney cells (HEK293T cells) were transfected with a Flag-ChREBP plasmid to explore ChREBP acetylation. Triglyceride (TG) and glucose concentrations and enzymatic activities were measured in the intestine and IECs of yellow catfish. They also were subjected to immunofluorescence, immunoprecipitation, qPCR, and immunoblotting. Immunoblotting and immunoprecipitation were performed with HEK293T cells. Results The G group had greater intestine TGs (0.99- to 2.30-fold); activities of glucose 6-phospate dehydrogenase, 6-phosphogluconate dehydrogenase, and isocitrate dehydrogenase (0.12- to 2.10-fold); and expression of lipogenic genes (0.32- to 2.34-fold) than the CS, PS, and D groups. The G group had greater intestine sglt1/2 mRNA and protein expression than the CS, S and D groups (0.35- to 1.12-fold and 0.40- to 4.67-fold, respectively), but lower mRNA amounts of lipolytic genes (48.6%–65.8%) than the CS and PS groups. LX-4211 alleviated the glucose-induced increase in sglt1/2 mRNA (38.2%–47.4%) and SGLT1 protein (48.0%) expression, TGs (29.3%), and lipogenic enzyme activities (27.7%–42.1%) and gene expression (38.0%–55.5%) in the IECs. TBSA promoted the glucose-induced increase in TGs (11.3%), fatty acid synthase activity (32.6%), and lipogenic gene expression (21.6%–34.4%) in the IECs and acetylated ChREBP (10.5%) in HEK293T cells. Conclusions SGLT1/2 signaling and acetylated ChREBP mediated glucose-induced changes in glucose absorption and lipid metabolism in the intestine and IECs of yellow catfish.

scholarly journals Simultaneous Exposure to Escherichia coli Heat-Labile and Heat-Stable Enterotoxins Increases Fluid Secretion and Alters Cyclic Nucleotide and Cytokine Production by Intestinal Epithelial Cells

2014 ◽  
Vol 82 (12) ◽  
pp. 5308-5316 ◽  
Author(s):  
Lisa T. Read ◽  
Rachel W. Hahn ◽  
Carli C. Thompson ◽  
David L. Bauer ◽  
Elizabeth B. Norton ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Epithelial Cells ◽  
Diarrheal Disease ◽  
Water Movement ◽  
Intestinal Epithelial Cells ◽  
Intestinal Lumen ◽  
Intestinal Epithelial ◽  
Simultaneous Exposure ◽  
Heat Stable ◽  
Heat Labile

ABSTRACTEnterotoxigenicEscherichia coli(ETEC) is a significant cause of diarrheal disease and death, especially in children in developing countries. ETEC causes disease by colonizing the small intestine and producing heat-labile toxin (LT), heat-stable toxin (ST), or both LT and ST (LT+ST). The majority of ETEC strains produce both ST and LT. Despite the prevalence of LT+ST-producing organisms, few studies have examined the physiologic or immunologic consequences of simultaneous exposure to these two potent enterotoxins. In the current report, we demonstrate that when LT and ST are both present, they increase water movement into the intestinal lumen over and above the levels observed with either toxin alone. As expected, cultured intestinal epithelial cells increased their expression of intracellular cyclic GMP (cGMP) when treated with ST and their expression of intracellular cyclic AMP (cAMP) when treated with LT. When both toxins were present, cGMP levels but not cAMP levels were synergistically elevated compared with the levels of expression caused by the corresponding single-toxin treatment. Our data also demonstrate that the levels of inflammatory cytokines produced by intestinal epithelial cells in response to LT are significantly reduced in animals exposed to both enterotoxins. These findings suggest that there may be complex differences between the epithelial cell intoxication and, potentially, secretory outcomes induced by ETEC strains expressing LT+ST compared with strains that express LT or ST only. Our results also reveal a novel mechanism wherein ST production may reduce the hosts' ability to mount an effective innate or adaptive immune response to infecting organisms.

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