南方医科大学学报

南方医科大学学报 ›› 2006, Vol. 26 ›› Issue (07): 1030-1033.

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钙介导As2O3诱导的线粒体通透性转变孔道开放

乔东访； 马安德； 晏芳； 王慧君；   

  1. 南方医科大学分析测试中心； 南方医科大学组织学与胚胎学教研室； 南方医科大学法医学研究所 广东广州510515； 广东广州510515；
  • 出版日期:2006-07-20 发布日期:2006-07-20

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

QIAO Dong-fang1, MA An-de1, YAN Fang2, WANG Hui-jun3 1Instrumental Analysis and Research Center, 2Department of Histology and Embryology, 3Institute of Forensic Medicine, Southern Medical University, Guangzhou 510515, China   

  1. 南方医科大学分析测试中心； 南方医科大学组织学与胚胎学教研室； 南方医科大学法医学研究所 广东广州510515； 广东广州510515；
  • Online:2006-07-20 Published:2006-07-20

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摘要： 目的研究Ca2+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/LAs2O3加10μmol/LCa2+处理线粒体,PTP开放。单独使用10μmol/LAs2O3处理,或先用0.5mmol/LEGTA螯合Ca2+,然后用10μmol/LAs2O3加10μmol/LCa2+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/LCa2+介导。结论Ca2+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Ca2+阈值促使PTP开放,有可能通过调节细胞内的Ca2+来调控线粒体PTP开放进而调控细胞凋亡。?更多还原

Abstract: Objective To explore the mechanism of arsenite-induced permeability transition pore (PTP) opening and the role of Ca2+ in As2O3-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 mitochondia was measured with fluorescence spectrophotometry. Results PTP opening was induced with 10 μmol/L As2O3 in the presence of 10 μmol/L Ca2+, and the absorbance at 540 nm of the mitochondria did not decrease in response to exclusive treatment with 10 μmol/L As2O3, or to 10 μmol/L As2O3 plus 10 μmol/L Ca2+ treatment with 0.5 mmol/L EGTA pretreatment. Treatment with As2O3 at 0, 5, 10 and 20 μmol/L in the presence of 50, 20, 10 and 5 μmol/L Ca2+, respectively, resulted in decreased absorbance at 540 nm of the mitochondria. Conclusion Ca2+ mediates As2O3-induced PTP opening. As2O3 lowers Ca2+ threshold necessary for eliciting PTP opening and thereby regulates cell apoptosis.

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