Taurocholate Potentiates Ethanol-Induced NF-κB Activation and Inhibits Caspase-3 Activity in Cultured Rat Gastric Mucosal Cells
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We have previously shown that ethanol (EtOH) induces protective NF-κB 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-κB 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-κB 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-κB signaling.
KeywordsNF-κB Acetylsalicylic acid Taurocholate gastric mucosa Apoptosis
Supported by Helsinki University Central Hospital Research Funds (EVO); Helsinki, Finland, Helsinki University Research Funds, Helsinki, Finland; Jenny and Antti Wihuri Foundation, Helsinki, Finland and Biomedicum Research Foundation, Helsinki, Finland. The authors thank Mrs. Sanna Vainionpää and Mrs. Paula Kokko for valuable technical assistance.
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