Thapsigargin directly induces the mitochondrial permeability transition

被引：54

作者：

Korge, P

Weiss, JN

机构：

[1] Univ Calif Los Angeles, Sch Med, Div Cardiol, Dept Med Cardiol,Cardiovasc Res Lab, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, Sch Med, Dept Physiol, Cardiovasc Res Lab, Los Angeles, CA 90095 USA

来源：

EUROPEAN JOURNAL OF BIOCHEMISTRY | 1999年 / 265卷 / 01期

关键词：

mitochondria; permeability transition pore; calcium; thapsigargin;

D O I：

10.1046/j.1432-1327.1999.00724.x

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

High concentrations of thapsigargin (TG) have been used to study the; process of necrotic cell death, which involves mitochondria in the cell rapidly undergoing the mitochondrial permeability transition (MPT). We therefore investigated the effects of TG on MPT in isolated liver and heart mitochondria. Using a matrix swelling assay in combination with a novel enzymatic method based on inner membrane permeability to citrate synthase substrates, TG induced MPT in a concentration-dependent manner, independent of extramitochondrial [Ca2+] and inhibitable by cyclosporin A. Evidence from alamethicin-permeabilized mitochondria suggests that TG induces MPT by causing Ca2+ release from mitochondrial matrix Ca2+-binding sites. These findings suggest that the MPT-inducing effect of TG may contribute to its pro-necrotic and pro-apoptotic effects in various cell types.

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收藏

页码：273 / 280

页数：8

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