Abstract |
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.
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Authors | Y Park, T M Devlin, D P Jones |
Journal | Toxicology and applied pharmacology
(Toxicol Appl Pharmacol)
Vol. 126
Issue 1
Pg. 33-8
(May 1994)
ISSN: 0041-008X [Print] United States |
PMID | 8184430
(Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Phosphates
- Prostaglandins B
- di-Calciphor
- Antimycin A
- Adenosine Triphosphate
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Topics |
- Adenosine Triphosphate
(metabolism)
- Animals
- Antimycin A
(antagonists & inhibitors, toxicity)
- Cell Death
(drug effects)
- In Vitro Techniques
- Liver
(cytology, drug effects, metabolism)
- Male
- Membrane Potentials
(drug effects)
- Mitochondria, Liver
(drug effects)
- Phosphates
(metabolism)
- Prostaglandins B
(pharmacology)
- Rats
- Rats, Sprague-Dawley
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