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Cyclosporine A protects mitochondria in an in vitro model of hypoxia/reperfusion injury
Author(s) -
Gogvadze Vladimir,
Richter Christoph
Publication year - 1993
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(93)80682-k
Subject(s) - hypoxia (environmental) , mitochondrion , in vitro , reperfusion injury , pharmacology , chemistry , microbiology and biotechnology , medicine , biochemistry , ischemia , biology , cardiology , oxygen , organic chemistry
Hypoxia/reperfusion injury is a major clinical problem. One of its hallmarks is an increased cytosolic Ca 2+ content and an increased generation of reactive oxygen species in the cytosol and in mitochondria. In the present study of an in vitro model of hypoxia/reperfusion injury, mitochondria are exposed to Ca 2+ in combination with extra‐ and intramitochondrially acting prooxidants. In this model mitochondria are damaged in a Ca 2+ ‐dependent manner. The extent and the site(s) of damage depend on both the kind of respiratory substrate and prooxidant used. The major damage occurs specifically at site I of the respiratory chain, and is due to hydrolysis of oxidized pyridine nucleotides and Ca 2+ release followed by Ca 2+ re‐uptake (Ca 2+ ‘cycling’). Cyclosporine A completely protects against this damage. The protection is due to inhibition of pyridine nucleotide hydrolysis, an obligatory step in the sequence of events that links prooxidants to Ca 2+ release from intact mitochondria.