Taurocholate potentiates ethanol-induced NF-kappaB activation and inhibits caspase-3 activity in cultured rat gastric mucosal cells.
We have previously shown that ethanol (EtOH) induces protective NF-kappaB activation in gastric surface epithelial cells. This study investigates the defense systems in rat gastric mucosal cells (RGM-1) exposed simultaneously to EtOH and taurocholate (TC) or acetylsalicylic acid (ASA). Simultaneous exposure to ASA and EtOH increased EtOH-induced caspase-3 activity and decreased cell viability, indicating synergetic damaging action. Simultaneous exposure to TC (5 mM) with EtOH (5%) increased EtOH-induced NF-kappaB activation, opposing EtOH-induced decrease in cell membrane integrity and in cell viability as shown by decreasing RelA expression with siRNA technique. Low doses of TC decreased the EtOH (5%) induced caspase-3 activity independently from NF-kappaB pathway and inhibited EtOH-induced decrease in caspase-3 precursor protein levels, also indicating the inhibition of caspase-3 pathway. The TC (5 mM)-induced protection in EtOH exposed tissues seems to have two distinct pathways, inhibition of apoptosis and enhancement of NF-kappaB signaling.
Mustonen
Harri
H
Department of Surgery, Helsinki University Central Hospital, Box 700, 00029, HUS, Helsinki, Finland. harri.mustonen@helsinki.fi
Puolakkainen
Pauli
P
Kemppainen
Esko
E
Kiviluoto
Tuula
T
Kivilaakso
Eero
E
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001241:Aspirin / Q000633:toxicity; D053148:Caspase 3 / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004847:Epithelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D000431:Ethanol / Q000633:toxicity*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D013656:Taurocholic Acid / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000378:metabolism
D016328:NF-kappa B; D034741:RNA, Small Interfering; C498145:Rela protein, rat; D051996:Transcription Factor RelA; D000431:Ethanol; D013656:Taurocholic Acid; C505410:Casp3 protein, rat; D053148:Caspase 3; D001241:Aspirin