Preconditioning with cobalt protoporphyrin protects human gastric mucosal cells from deoxycholate-induced apoptosis

In this study, a known inducer of heme oxygenase-1 (HO-1) expression, cobalt protoporphyrin, and the introduction of a recombinant plasmid expressing HO-1 were examined for their ability to protect gastric epithelial cells from deoxycholate-induced injury. Physiologic levels of the secondary bile salt induce apoptosis in a human gastric adenocarcinoma mucosal cell line. Cobalt protoporphyrin induced expression of HO-1 protein with maximal levels attaining a plateau at 48 hours. Pretreatment with cobalt protoporphyrin before challenge with 200 μM deoxycholate inhibited cell death, DNA fragmentation, the appearance of cytosolic nucleosomes, and cleavage of caspase-3, caspase-9, and poly-(ADP-ribose) polymerase 1. Similarly, expression of HO-1 by introduction of a recombinant plasmid also showed a resistance to deoxycholate-induced apoptosis. These results implicate a possible role for HO-1 in modulating apoptosis in gastric epithelial cells.