title: Preconditioning with cobalt protoporphyrin protects human gastric mucosal cells from deoxycholate-induced apoptosis.
abstract: 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.
authors.affiliation: Department of Physiology and Biophysics, Medical College of Virginia, Campus of Virginia Commonwealth University, Richmond, Virginia, USA.
authors.forename: Tina E
authors.initials: TE
authors.lastname: Lawson
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Redlak
authors.forename: Dorne R
authors.initials: DR
authors.lastname: Yager
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002756:Cholagogues and Choleretics / Q000009:adverse effects*; D019610:Cytoprotection; D053938:DNA Fragmentation / Q000187:drug effects; D003840:Deoxycholic Acid / Q000009:adverse effects*; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology*; D051547:Heme Oxygenase-1 / Q000502:physiology; D006801:Humans; D009707:Nucleosomes / Q000473:pathology; D010957:Plasmids / Q000378:metabolism; D011524:Protoporphyrins / Q000494:pharmacology*; D014162:Transfection
chemical_list: D002756:Cholagogues and Choleretics; D009707:Nucleosomes; D011524:Protoporphyrins; D003840:Deoxycholic Acid; C007095:cobaltiprotoporphyrin; D051547:Heme Oxygenase-1; D020169:Caspases