Premium
Survivin is a key factor in the differential susceptibility of gastric endothelial and epithelial cells to alcohol‐induced injury
Author(s) -
Jones Michael K.,
Padilla Oscar R.,
Zhu Ercheng,
Ngov Melisa
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.979.7
Subject(s) - survivin , apoptosis , cancer research , transfection , chemistry , biology , cell culture , biochemistry , genetics
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