Gogvadze V, Richter C
Laboratory of Biochemistry I, Swiss Federal Institute of Technology (ETH), Zürich.
FEBS Lett. 1993 Nov 1;333(3):334-8. doi: 10.1016/0014-5793(93)80682-k.
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 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 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.
缺氧/再灌注损伤是一个主要的临床问题。其特征之一是胞质Ca2+含量增加，以及胞质和线粒体中活性氧生成增加。在本缺氧/再灌注损伤体外模型研究中，线粒体暴露于Ca2+，并与线粒体外和线粒体内起作用的促氧化剂联合作用。在该模型中，线粒体以Ca(2+)依赖的方式受损。损伤的程度和部位取决于所使用的呼吸底物和促氧化剂的种类。主要损伤特别发生在呼吸链的位点I，是由于氧化吡啶核苷酸的水解和Ca2+释放，随后是Ca2+再摄取（Ca2+“循环”）。环孢素A完全防止这种损伤。这种保护作用是由于抑制了吡啶核苷酸水解，这是将促氧化剂与完整线粒体中Ca2+释放联系起来的一系列事件中的一个必要步骤。
