Protection of hepatocytes against death due to mitochondrial failure: effect of di-Calciphor on antimycin A-induced toxicity.
Di-Calciphor is a synthetic derivative of prostaglandin B1 that protects against cerebral and cardiac ischemia apparently by preserving mitochondrial function. To determine whether di-Calciphor specifically protects against mitochondrial failure, we studied its effects on mitochondrial functions in hepatocytes treated with the specific mitochondrial poison, antimycin A. The results show that 1 microM di-Calciphor protects against cell death at concentrations of antimycin A that inhibited mitochondrial respiration and caused cellular ATP depletion. Di-Calciphor did not protect against loss of ATP but did protect against the loss of mitochondrial delta psi and delta pH. In addition, di-Calciphor protected against antimycin A-induced loading of phosphate into mitochondria and an associated mitochondrial swelling. Thus, these results show that di-Calciphor protects against a specific mitochondrial poison and support the interpretation that di-Calciphor is a mitochondrial protective agent. In addition, the results suggest that the protection of the mitochondria involves preservation of mitochondrial ionic and osmotic stability and does not involve improved ATP supply.
Park
Y
Y
Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322.
Devlin
T M
TM
Jones
D P
DP
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000968:Antimycin A / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D016923:Cell Death / Q000187:drug effects; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects*; D010710:Phosphates / Q000378:metabolism; D011456:Prostaglandins B / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D010710:Phosphates; D011456:Prostaglandins B; C076722:di-Calciphor; D000968:Antimycin A; D000255:Adenosine Triphosphate