Bellomo G, Fulceri R, Albano E, Gamberucci A, Pompella A, Parola M, Benedetti A
Dipartimento di Medicina Interna e Terapia Medica, University of Pavia, Italy.
Cell Calcium. 1991 May;12(5):335-41. doi: 10.1016/0143-4160(91)90049-k.
The alterations of mitochondrial membrane potential during the development of irreversible cell damage were investigated by measuring rhodamine-123 uptake and distribution in primary cultures as well as in suspensions of rat hepatocytes exposed to different toxic agents. Direct and indirect mechanisms of mitochondrial damage have been identified and a role for Ca2+ in the development of this type of injury by selected compounds was assessed by using extracellular as well as intracellular Ca2+ chelators. In addition, mitochondrial uncoupling by carbonylcyanide-m-chloro-phenylhydrazone (CCCP) resulted in a marked depletion of cellular ATP that was followed by an increase in cytosolic Ca2+ concentration, immediately preceding cell death. These results support the existence of a close relationship linking, in a sort of reverberating circuit, the occurrence of mitochondrial dysfunction and the alterations in cellular Ca2+ homeostasis during hepatocyte injury.
通过测量罗丹明123在原代培养物以及暴露于不同毒性剂的大鼠肝细胞悬浮液中的摄取和分布，研究了不可逆细胞损伤发展过程中线粒体膜电位的变化。已经确定了线粒体损伤的直接和间接机制，并通过使用细胞外以及细胞内钙离子螯合剂评估了钙离子在某些化合物导致的这类损伤发展过程中的作用。此外，羰基氰化物间氯苯腙（CCCP）引起的线粒体解偶联导致细胞ATP显著耗竭，随后在细胞死亡之前胞质钙离子浓度升高。这些结果支持在肝细胞损伤期间，线粒体功能障碍的发生与细胞钙离子稳态改变之间存在紧密联系，这种联系以一种反馈回路的形式存在。
