RRC ID 18996
Author Jones MK, Padilla OR, Zhu E.
Title Survivin is a key factor in the differential susceptibility of gastric endothelial and epithelial cells to alcohol-induced injury.
Journal J. Physiol. Pharmacol.
Abstract We previously demonstrated that the anti-apoptosis protein, survivin, plays a protective role against alcohol-induced gastric injury. Since the endothelium 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 (RGM1 cells, an epithelial cell line derived from normal rat gastric mucosa) expressed 7.5-fold greater survivin protein levels vs. rat gastric endothelial cells. Survivin expression correlated with resistance of gastric epithelial vs. endothelial cells to both alcohol-induced cell damage and alcohol-induced apoptosis. Suppression of survivin protein expression levels using siRNA rendered the gastric epithelial cells as susceptible to both alcohol-induced cell damage and apoptosis as the gastric endothelial cells. Conversely, forced overexpression of survivin by transient transfection rendered gastric endothelial cells as resistant to both alcohol-induced cell damage and apoptosis as mock-transfected gastric epithelial cells. Moreover, overexpression of a threonine-34 to glutamate phosphorylation mimic mutant survivin construct rendered gastric endothelial cells significantly more resistant to alcohol-induced damage and apoptosis vs. mock-transfected gastric epithelial cells. These findings indicate that disparate survivin expression levels can explain the discrepancy between gastric epithelial and endothelial cell susceptibility to alcohol-induced injury; and, that a negative charge at amino acid residue 34 on survivin, such as that which naturally occurs by phosphorylation of threonine-34, enhances its property in conferring gastric mucosal protection.
Volume 61(3)
Pages 253-64
Published 2010-6
PMID 20610854
PMC PMC2953945
MeSH Alcohol-Induced Disorders / metabolism* Alcohol-Induced Disorders / pathology Animals Apoptosis Cell Line Disease Susceptibility Endothelial Cells / drug effects* Endothelial Cells / metabolism Endothelial Cells / pathology Epithelial Cells / drug effects* Epithelial Cells / metabolism Epithelial Cells / pathology Ethanol / toxicity* Gastric Mucosa / drug effects* Gastric Mucosa / metabolism Gastric Mucosa / pathology Male Microtubule-Associated Proteins / genetics Microtubule-Associated Proteins / metabolism* Rats Stomach Diseases / chemically induced Stomach Diseases / metabolism* Stomach Diseases / pathology Survivin Transfection
IF 2.544
Times Cited 10
Human and Animal Cells RGM1 (RCB0876)