Effect of nitric oxide on apoptotic activity in the rat gastrointestinal tract.
The effect of nitric oxide (NO) on apoptosis in the gastrointestinal mucosa was investigated. Experiments involved long-term exposure of rat gastric mucosal cells in vitro to exogenous NO delivered from the NO, donor S-nitroso-N-acetyl-penicillamine, and the effect of intravenous administration of lipopolysaccharide in vivo, in the presence and absence of the selective inhibitor of inducible NO synthase N-(3-(aminomethyl)benzyl) acetamidine (1400 W). S-nitroso-N-acetyl-penicillamine produced a dose-related inhibition of caspase 3-like activity and DNA fragmentation in isolated gastric mucosal cells. Caspase 3-like activity and DNA fragmentation in gastric, ileal and colonic mucosa were increased both 5 and 24 h after injection of lipopolysaccharide (3 mg/kg, i.v.) to rats in vivo. Administration of 1400 W (5 mg/kg, i.v.) immediately after lipopolysaccharide enhanced caspase 3-like activity and DNA fragmentation above that found with lipopolysaccharide alone. In conclusion, data obtained both in vitro and in vivo suggest that NO exerts an anti-apoptotic effect on rat gastrointestinal mucosal cells.
Bersimbaev
R I
RI
Department of Molecular Biology and Genetics, Faculty of Biology, Kazakh State National University, Almaty, Kazakhstan. riber@itte.kz
Yugai
Y E
YE
Hanson
P J
PJ
Tzoy
I G
IG
D000578:Amidines / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001596:Benzylamines / Q000494:pharmacology; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D003106:Colon / Q000187:drug effects / Q000201:enzymology; D053938:DNA Fragmentation / Q000187:drug effects; D004064:Digestive System / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects; D007082:Ileum / Q000187:drug effects / Q000201:enzymology; D020287:In Situ Nick-End Labeling; D007275:Injections, Intravenous; D007413:Intestinal Mucosa / Q000187:drug effects / Q000201:enzymology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D026423:S-Nitroso-N-Acetylpenicillamine; D013997:Time Factors
D000578:Amidines; D001596:Benzylamines; D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; C104820:N-(3-(aminomethyl)benzyl)acetamidine; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D010396:Penicillamine