Cyclosporine A protects mitochondria in an in vitro model of hypoxia/reperfusion injury

FEBS Letters

Gogvadze, Vladimir¹  Richter, Christoph¹ 

[1] Laboratory of Biochemistry I, Swiss Federal Institute of Technology (ETH), Universitätstr. 16, CH-8092 Zürich, Switzerland

关键词: Reactive oxygen;    Calcium;    Pyridine nucleotide;    Rat liver;    CSA;    Cyclosporine A;    EGTA;    ethylene glycol bis(β-aminoethyl ether)-N;    N;    N';    N'-tetraacetic acid;    CCCP;    carbonyl cyanide m-chlorophenylhydrazone;    HRI;    hypoxia/reperfusion injury;    RCI;    respiratory control index;    tbh;    t-butylhydroperoxide;    XO/HX/Fe;    xanthine oxidase/hypoxanthine/iron ions;   

DOI  :  10.1016/0014-5793(93)80682-K

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Hypoxia/reperfusion injury is a major clinical problem. One of its hallmarks is an increased cytosolic Ca²⁺ 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 Ca²⁺ in combination with extra- and intramitochondrially acting prooxidants. In this model mitochondria are damaged in a Ca²⁺-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 Ca²⁺ release followed by Ca²⁺ re-uptake (Ca²⁺ ‘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 Ca²⁺ release from intact mitochondria.

【 授权许可】

Unknown