Abstract

We previously demonstrated that the anti‐apoptosis protein, survivin, plays a protective role against alcohol‐induced gastric injury. Since the endothelia is a primary target of alcohol‐induced gastric damage, we investigated whether survivin expression is a key factor in the greater susceptibility of gastric endothelial vs. epithelial cells to alcohol‐induced injury. Here, we demonstrate that rat gastric epithelial cells expressed 8‐fold (P<0.01) greater survivin levels vs. rat gastric endothelial cells. Survivin expression correlated (r=0.84, P<0.05) with resistance of gastric epithelial vs. endothelial cells to both alcohol‐induced cell damage (20 ± 3% vs. 65 ± 7%, P<0.05) and alcohol‐induced apoptosis (14 ± 2% vs. 32 ± 4%, P<0.05). Forced overexpression of survivin in gastric endothelial cells significantly increased resistance to both alcohol‐induced damage and apoptosis. Moreover, overexpression of a threonine‐34 to glutamate mutant survivin construct rendered gastric endothelial cells significantly more resistant to alcohol‐induced damage and apoptosis vs. non‐transfected gastric epithelial cells (P<0.05). These findings indicate that disparate survivin expression levels can explain the discrepancy between gastric epithelial and endothelial cell susceptibility to alcohol‐induced injury; and, survivin phosphorylation is important in mediating gastric mucosal protection.NIH R01AA14946

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