Calcium accentuates injury induced by ethanol in human gastric cells.
The mechanism(s) whereby ethanol induces cellular injury remains poorly understood. Furthermore, the role of calcium in gastric mucosal injury under in vitro conditions is poorly defined. The major objectives of this study were to (1) define the temporal relationship between intracellular calcium accumulation induced by ethanol and cellular injury, (2) characterize the mechanism(s) whereby ethanol increases cellular calcium content, and (3) determine whether calcium removal would attenuate ethanol-induced cellular injury. Human gastric cells (AGS) were used for all experiments. Sustained intracellular calcium accumulation induced by ethanol, but not transient changes, preceded and directly correlated with cellular injury. Cells exposed to damaging concentrations of ethanol demonstrated an initial calcium surge that appeared to be a consequence of inositol 1,4,5-triphosphate (IP3) generation and subsequent internal store release followed by a sustained plateau resulting from extracellular calcium influx through store-operated calcium channels. Finally, both morphologic (cellular injury) and functional (clearance of bovine serum albumin) changes induced by ethanol were significantly attenuated when extracellular Ca(+&plus) influx was prevented, and further decreased when intracellular Ca(++) stores were depleted. These data indicate that calcium plays a significant role in cellular injury induced by ethanol.
Kokoska
E R
ER
Theodore Cooper Surgical Research Institute, Department of Surgery, Saint Louis University Health Sciences Center, St. Louis, MO 63104, USA.
Smith
G S
GS
Deshpande
Y
Y
Wolff
A B
AB
Rieckenberg
C
C
Miller
T A
TA
D000704:Analysis of Variance; D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects; D020013:Calcium Signaling / Q000187:drug effects; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000009:adverse effects*; D004996:Ethidium / Q000031:analogs & derivatives; D005456:Fluorescent Dyes; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007364:Intercalating Agents; D007811:Lanthanum / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D012710:Serum Albumin, Bovine; D019284:Thapsigargin / Q000494:pharmacology; D013997:Time Factors; D014700:Verapamil / Q000494:pharmacology; D014966:Xanthenes
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D007364:Intercalating Agents; D014966:Xanthenes; C028521:lanthanum chloride; D012710:Serum Albumin, Bovine; D000431:Ethanol; C018533:ethidium homodimer; D019284:Thapsigargin; D007811:Lanthanum; C034657:Texas red; D015544:Inositol 1,4,5-Trisphosphate; D014700:Verapamil; D000252:Calcium-Transporting ATPases; D004996:Ethidium; D009543:Nifedipine; D002118:Calcium