Park Y, Devlin T M, Jones D P
Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322.
Toxicol Appl Pharmacol. 1994 May;126(1):33-8. doi: 10.1006/taap.1994.1087.
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.
双钙磷素是前列腺素B1的合成衍生物，它显然通过维持线粒体功能来预防脑和心脏缺血。为了确定双钙磷素是否能特异性预防线粒体功能衰竭，我们研究了其对用特异性线粒体毒物抗霉素A处理的肝细胞中线粒体功能的影响。结果表明，在抑制线粒体呼吸并导致细胞ATP耗竭的抗霉素A浓度下，1微摩尔双钙磷素可预防细胞死亡。双钙磷素不能预防ATP的损失，但能预防线粒体膜电位差和pH值差的损失。此外，双钙磷素可预防抗霉素A诱导的磷酸盐向线粒体的积聚以及相关的线粒体肿胀。因此，这些结果表明双钙磷素可预防一种特异性线粒体毒物，并支持双钙磷素是一种线粒体保护剂的解释。此外，结果表明对线粒体的保护涉及维持线粒体的离子和渗透稳定性，而不涉及改善ATP供应。
