Protection of Gastric Mucosal Cells from Apoptosis and Necrosis by Induction of HSP and PGE₂

Abstract

Various gastric irritants induce cell death of gastric mucosal cells, resulting in gastric ulcers in vivo. We recently reproduced gastric irritant-induced cell death in vitro, using primary cultures of guinea pig gastric mucosal cells. We found that the short-term treatment of cells with relatively high concentrations of irritants or the long-term treatment of cells with relatively low concentrations of irritants induce necrosis or apoptosis, respectively. We also reproduced the spontaneous apoptosis of matured gastric mucosal cells at gastric surface and found that the apoptosis-inducing pathway of this spontaneous apoptosis is different from that of the irritant-induced apoptosis. Heat shock proteins (HSPs) are known to make cells non-specifically resistant to various irritants. We found that preinduction of HSPs by geranylgeranylacetone or a low concentration of ethanol protects gastric mucosal cells from both apoptosis and necrosis induced by various gastric irritants. Therefore, non-toxic HSP-inducers, such as geranylgeranylacetone, seem to be clinically beneficial for gastric irritant-induced gastric ulcers.