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.
- 1.Mustonen H, Kiviluoto T, Puolakkainen P, Kivilaakso E. Heat shock inhibits ethanol-induced NF-B activation in cultured rat gastric mucosal cells. Gastroenterology. 2005;128:A-599.Google Scholar
- 10.Konturek PC, Kania J, Gessner U, Konturek SJ, Hahn EG, Konturek JW. Effect of vitamin C-releasing acetylsalicylic acid on gastric mucosal damage before and after Helicobacter pylori eradication therapy. Eur J Pharmacol. 2004;506:169–177. doi: 10.1016/j.ejphar.2004.10.048.PubMedCrossRefGoogle Scholar
- 14.Puurunen J, Huttunen P, Hirvonen J. Interactions between ethanol and acetylsalicylic acid in damaging the rat gastric mucosa. Acta Pharmacol Toxicol. 1983;52:321–327.Google Scholar