Rolo A P, Oliveira P J, Moreno A J, Palmeira C M
Center for Neurosciences and Cell Biology of Coimbra, Department of Zoology, University of Coimbra, Portugal.
Biosci Rep. 2001 Feb;21(1):73-80. doi: 10.1023/a:1010438202519.
Several reports support the concept that bile acids may be cytotoxic during cholestatic disease process by causing mitochondrial dysfunction. Here we report additional data and findings aimed at a better understanding of the involvement of the permeability transition pore (PTP) opening in bile acids toxicity. The mitochondrial PTP is implicated as a mediator of cell injury and death in many situations. In the presence of calcium and phosphate, chenodeoxycholic acid (CDCA) induced a permeability transition in freshly isolated rat liver mitochondria, characterized by membrane depolarization, release of matrix calcium, and osmotic swelling. All these events were blocked by cyclosporine A (CyA) and the calcium uniporter inhibitor ruthenium red (RR). The results suggest that CDCA increases the sensitivity of isolated mitochondria in vitro to the calcium-dependent induction of the PTP.
几份报告支持这样一种观点，即胆汁酸在胆汁淤积性疾病过程中可能通过导致线粒体功能障碍而具有细胞毒性。在此，我们报告了更多的数据和发现，旨在更好地理解通透性转换孔（PTP）开放在胆汁酸毒性中的作用。线粒体PTP在许多情况下被认为是细胞损伤和死亡的介质。在存在钙和磷酸盐的情况下，鹅去氧胆酸（CDCA）诱导新鲜分离的大鼠肝线粒体发生通透性转换，其特征为膜去极化、基质钙释放和渗透性肿胀。所有这些事件均被环孢素A（CyA）和钙单向转运体抑制剂钌红（RR）阻断。结果表明，CDCA在体外增加了分离线粒体对钙依赖性PTP诱导的敏感性。
