Role of calcium in adaptive cytoprotection and cell injury induced by deoxycholate in human gastric cells.
We have developed an in vitro model of adaptive cytoprotection induced by deoxycholate (DC) in human gastric cells and have shown that pretreatment with a low concentration of DC (mild irritant, 50 microM) significantly attenuates injury induced by a damaging concentration of DC (250 microM). This study was undertaken to assess the effect of the mild irritant on changes in intracellular Ca2+ and to determine if these perturbations account for its protective action. Protection conferred by the mild irritant was lost when any of its effects on intracellular Ca2+ were prevented: internal Ca2+ store release via phospholipase C and inositol 1,4, 5-trisphosphate sustained Ca2+ influx through store-operated Ca2+ channels or eventual Ca2+ efflux. We also investigated the relationship between Ca2+ accumulation and cellular injury induced by damaging concentrations of DC. In cells exposed to high concentrations of DC, sustained Ca2+ accumulation as a result of extracellular Ca2+ influx, but not transient changes in intracellular Ca2+ content, appeared to precede and induce cellular injury. We propose that the mild irritant disrupts normal Ca2+ homeostasis and that this perturbation elicits a cellular response (involving active Ca2+ efflux) that subsequently provides a protective action by limiting the magnitude of intracellular Ca2+ accumulation.
Kokoska
E R
ER
Theodore Cooper Surgical Research Institute, Department of Surgery, Saint Louis University Health Sciences Center, St. Louis, Missouri 63104, USA.
Smith
G S
GS
Wolff
A B
AB
Deshpande
Y
Y
Rieckenberg
C L
CL
Banan
A
A
Miller
T A
TA
D000064:Acclimatization; D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003840:Deoxycholic Acid / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004963:Estrenes / Q000494:pharmacology; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D007811:Lanthanum / Q000494:pharmacology; D018613:Microscopy, Confocal; D009355:Neomycin / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D011794:Quercetin / Q000494:pharmacology; D013274:Stomach Neoplasms; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology
D004963:Estrenes; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D003840:Deoxycholic Acid; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D007811:Lanthanum; D011794:Quercetin; D014700:Verapamil; D010738:Type C Phospholipases; D009355:Neomycin; D009543:Nifedipine; D002118:Calcium