钙介导As2O3诱导的线粒体通透性转变孔道开放

目的研究Ca^2＋在AS2O3介导的PTP开放中的作用，探讨AS2O3诱导粒体通透性转变孔道（PTP）开放的机制。方法提取大鼠肝线粒体，通过紫外分光光度仪检测Res作用下线粒体的膨胀，借此测定线粒体PTP的开放状态；借助荧光探针Rh123检测线粒体膜电位的变化。结果用10μmol／L，加10μmol／LCa^2＋处理线粒体，PTP开放。单独使用10μmol／LAS2O3处理，或先用0．5mmol／LEGTA螯合C矿，然后用10 mol／LAS2O3加10μmol／LCa^2＋处理，线粒体D540不下降。分别用0、5、10和20μmol／LAS2O3，处理线粒体，D540变化可分别被50、20、10和5μmol／LCa^2＋介导。结论C矿能介导AS2O3，诱导的PTP开放；AS2O3，诱导细胞凋亡通过降低诱发PTP开放所需的Ca^2＋阈值促使PTP开放，有可能通过调节细胞内的Ca^2＋来调控线粒体PTP开放进而调控细胞凋亡。

As2O3-induced permeability transition pore opening in mitochondria depends on Ca2+

OBJECTIVE: To explore the mechanism of arsenite-induced permeability transition pore (PTP) opening and the role of Ca(2+). in As(2)O(3)-induced PTP opening. METHOD: The mitochondria were prepared from Wistar rat liver and mitochondrial swelling was assessed spectrophotometrically at 540 nm to evaluate PTP opening. The membrane potential of the mitochondria was measured with fluorescence spectrophotometry. RESULTS: PTP opening was induced with 10 micromol/L As(2)O(3) in the presence of 10 micromol/L Ca(2+), and the absorbance at 540 nm of the mitochondria did not decrease in response to exclusive treatment with 10 micromol/L As(2)O(3), or to 10 micromol/L As(2)O(3) plus 10 micromol/L Ca(2+) treatment with 0.5 mmol/L EGTA pretreatment. Treatment with As(2)O(3) at 0, 5, 10 and 20 micromol/L in the presence of 50, 20, 10 and 5 micromol/L Ca(2+), respectively, resulted in decreased absorbance at 540 nm of the mitochondria. CONCLUSION: Ca(2+) mediates As(2)O(3)-induced PTP opening. As(2)O(3) lowers Ca(2+) threshold necessary for eliciting PTP opening and thereby regulates cell apoptosis.