State Key Laboratory of Virology, Ministry of Education, College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072, People's Republic of China.
J Membr Biol. 2011 May;241(1):39-49. doi: 10.1007/s00232-011-9361-y. Epub 2011 Apr 3.
The deleterious action of Cd2+ on rat liver mitochondria was investigated in this work using spectroscopic and microscopic methods. The concentration dependence of Cd2+ on mitochondrial swelling, membrane potential and membrane fluidity was studied. Our aim was to detect the active sites of Cd2+ in the mitochondrial membrane treatments with cyclosporin A (CsA) and EGTA on the mitochondrial permeability transition (MPT) induced by low and high concentrations of Cd2+. The protective effects of dithiothreitol, human serum albumin and monobromobimane+ on Cd2+-induced MPT were also monitored. All of these investigations indicated that Cd2+ can directly affect MPT at two separate localization sites at different concentrations: the classic Ca2+ triggering site and the thiol (-SH) groups of membrane proteins matched by MPT pore opening (defined as "S" site). At the high concentration of Cd2+, other free -SH groups in the mitochondrial matrix may be involved in this process. These findings were supported by transmission electron microscopy and shed light on the toxic mechanism of Cd2+ on mitochondria.
本研究采用光谱学和显微镜方法研究了 Cd2+对大鼠肝线粒体的有害作用。研究了 Cd2+浓度对线粒体肿胀、膜电位和膜流动性的影响。我们的目的是检测线粒体膜中 Cd2+的活性部位，并用环孢菌素 A（CsA）和 EGTA 处理，以检测低浓度和高浓度 Cd2+诱导的线粒体通透性转变（MPT）。还监测了二硫苏糖醇、人血清白蛋白和单溴代乙内酰脲+对 Cd2+诱导的 MPT 的保护作用。所有这些研究表明，Cd2+可以在两个不同的定位部位以不同的浓度直接影响 MPT：经典的 Ca2+触发部位和与 MPT 孔开放匹配的膜蛋白的巯基（-SH）基团（定义为“S”位）。在高浓度的 Cd2+下，线粒体基质中的其他游离 -SH 基团可能参与了这一过程。这些发现得到了透射电子显微镜的支持，并阐明了 Cd2+对线粒体的毒性作用机制。
