Taurocholate-induced nitric oxide signaling and the ensuing production of reactive oxygen species lead to an increase in epithelial permeability in cultivated mouse gastric epithelium.
We have here elucidated whether ulcerogenic agents affect the production of NO and reactive oxygen species (ROS). The ulcerogenic agents dose dependently induced NO and ROS production in mouse gastric epithelial cells. Taurocholate (TC, 5 mM) exposure did not affect cell viability, but it increased inducible nitric oxide synthase (iNOS) expression, NO production, ROS production, and epithelial permeability. Epithelial permeability was inhibited with NOS inhibitors or antioxidants. Oxidative stress induced by acetylsalicylic acid (ASA) and ethanol was not inhibited with NOS inhibitors. ASA induced ROS production even at low concentrations (1 mM), which did not affect cell viability. Ethanol-induced ROS production was linked to cell viability, suggesting direct oxidative stress caused by ethanol. Taurocholate-induced NO signaling and the ensuing production of ROS might contribute to initiation of defensive or adaptive cellular mechanisms. ASA-induced ROS signaling might have similar effects, whereas ethanol induced direct oxidative stress, having an influence on cell viability.
Mustonen
Harri
H
Department of Surgery, Helsinki University Central Hospital, Box 700, 00029 HUS, Helsinki, Finland. harri.mustonen@helsinki.fi
Kiviluoto
Tuula
T
Puolakkainen
Pauli
P
Paimela
Hannu
H
Mentula
Panu
P
Kemppainen
Esko
E
Kivilaakso
Eero
E
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002756:Cholagogues and Choleretics / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology; D005753:Gastric Mucosa / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D012997:Solvents / Q000494:pharmacology; D013656:Taurocholic Acid / Q000494:pharmacology*
D000975:Antioxidants; D002756:Cholagogues and Choleretics; D016861:Cyclooxygenase Inhibitors; D017382:Reactive Oxygen Species; D012997:Solvents; D009569:Nitric Oxide; D000431:Ethanol; D013656:Taurocholic Acid; D052247:Nitric Oxide Synthase Type II; D001241:Aspirin