共 38 条
Physiological concentrations of K+ inhibit cytochrome c-dependent formation of the apoptosome
被引:157
作者:

Cain, K
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机构:
Univ Leicester, MRC, Toxicol Unit, Leicester LE1 9HN, Leics, England Univ Leicester, MRC, Toxicol Unit, Leicester LE1 9HN, Leics, England

Langlais, C
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Univ Leicester, MRC, Toxicol Unit, Leicester LE1 9HN, Leics, England Univ Leicester, MRC, Toxicol Unit, Leicester LE1 9HN, Leics, England

Sun, XM
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机构:
Univ Leicester, MRC, Toxicol Unit, Leicester LE1 9HN, Leics, England Univ Leicester, MRC, Toxicol Unit, Leicester LE1 9HN, Leics, England

Brown, DG
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Univ Leicester, MRC, Toxicol Unit, Leicester LE1 9HN, Leics, England Univ Leicester, MRC, Toxicol Unit, Leicester LE1 9HN, Leics, England

Cohen, GM
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机构:
Univ Leicester, MRC, Toxicol Unit, Leicester LE1 9HN, Leics, England Univ Leicester, MRC, Toxicol Unit, Leicester LE1 9HN, Leics, England
机构:
[1] Univ Leicester, MRC, Toxicol Unit, Leicester LE1 9HN, Leics, England
关键词:
D O I:
10.1074/jbc.M107419200
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:
In many forms of apoptosis, cytochrome c released from mitochondria induces the oligomerization of Apaf-1 to form a caspase-activating apoptosome complex. Activation of lysates in vitro with dATP and cytochrome c results in the formation of an active caspase-processing similar to 700-kDa apoptosome complex, which predominates in apoptotic cells, and a relatively inactive similar to1.4-MDa complex. We now demonstrate that assembly of the active complex is suppressed by normal intracellular concentrations of K+. Using a defined apoptosome reconstitution system with recombinant Apaf-1 and cytochrome c, K+ also inhibits caspase activation by abrogating Apaf-1 oligomerization and apoptosome assembly. Once assembled, the apoptosome is relatively insensitive to the effects of ionic strength and processes/activates effector caspases. The inhibitory effects of K+ on apoptosome formation are antagonized in a concentration-dependent manner by cytochrome c. These studies support the hypothesis that the normal intracellular concentrations of K+ act to safeguard the cell against inappropriate formation of the apoptosome complex, caused by the inadvertent release of small amounts of cytochrome c. Thus, the assembly and activation of the apoptosome complex in the cell requires the rapid and extensive release of cytochrome c to overcome the inhibitory effects of normal intracellular concentrations of K+.
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页码:41985 / 41990
页数:6
相关论文
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Univ Leicester, MRC, Toxicol Unit, Leicester LE1 9HN, Leics, England Univ Leicester, MRC, Toxicol Unit, Leicester LE1 9HN, Leics, England

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