The temporal relationship between protein phosphatase, mitochondrial cytochrome c release, and caspase activation in apoptosis.
The temporal relationship between protein phosphatase, mitochondrial cytochrome c release, and caspase activation in apoptosis.
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细胞凋亡中蛋白磷酸酶、线粒体细胞色素 c 释放和 caspase 激活之间的时间关系。
DOI：
10.1006/excr.1998.4380
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发表时间：
1999
影响因子：
3.7
通讯作者：
Eastman,A
中科院分区：
文献类型：
--
作者：
Wolf,CM;Eastman,A
细胞凋亡是由蛋白酶的 caspase 家族成员介导的，该家族可以通过线粒体细胞色素的释放来激活。 caspase 家族的其他成员在细胞表面响应来自外部环境的直接刺激（例如通过 Fas 受体的激活）而被激活。有人建议，这些上游半胱天冬酶直接激活下游半胱天冬酶，这将消除 Fas 受体诱导的细胞色素蛋白凋亡的作用。我们证明，Jurkat 细胞线粒体响应星形孢菌素和激动性抗 Fas 抗体而释放细胞色素，并且只有后者被 caspase 抑制剂 z-VAD-FMK 抑制。这表明 Fas 介导的线粒体细胞色素 c 的释放需要上游 caspase，例如 caspase-8。蛋白磷酸酶抑制剂 calyculin A 阻止两种药物诱导的细胞色素 c 释放和细胞凋亡，表明两种模型中都需要细胞色素 c 的释放。锌曾经被认为是一种核酸内切酶抑制剂，此前已被证明可以阻止 caspase-3 的激活。我们发现锌可以阻止下游半胱天冬酶的激活和两种损伤诱导的细胞凋亡，但不能阻止线粒体细胞色素的释放。花萼蛋白 A 和锌阻止 DNA 消化的能力意味着线粒体途径对于两种药物诱导细胞凋亡都很重要。这些结果不支持 caspase-8 直接激活 caspase-3 的替代途径。这些结果还表明，关键的蛋白磷酸酶调节两种损伤诱导的细胞色素和细胞凋亡的释放。
Apoptosis is mediated by members of the caspase family of proteases which can be activated by release of mitochondrial cytochromec.Additional members of the caspase family are activated at the cell surface in response to direct stimulus from the external environment such as by activation of the Fas receptor. It has been suggested that these upstream caspases directly activate the downstream caspases which would obviate a role for cytochromecin apoptosis induced by the Fas receptor. We demonstrate that cytochromecis released from mitochondria of Jurkat cells in response to both staurosporine and an agonistic anti-Fas antibody and that only the latter is inhibited by the caspase inhibitor z-VAD-FMK. This suggests that an upstream caspase such as caspase-8 is required for the Fas-mediated release of mitochondrial cytochromec.The protein phosphatase inhibitor calyculin A prevented cytochromecrelease and apoptosis induced by both agents, suggesting that release of cytochromecis required in both models. Zinc, once thought of as an endonuclease inhibitor, has previously been shown to prevent the activation of caspase-3. We show that zinc prevents the activation of downstream caspases and apoptosis induced by both insults, yet does not prevent release of mitochondrial cytochromec.The ability of calyculin A and zinc to prevent DNA digestion implies that the mitochondrial pathway is important for induction of apoptosis by both agents. These results do not support an alternative pathway in which caspase-8 directly activates caspase-3. These results also demonstrate that a critical protein phosphatase regulates the release of cytochromecand apoptosis induced by both insults.
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细胞凋亡中蛋白磷酸酶、ICE/CED-3 蛋白酶、细胞内酸化和 DNA 碎片之间的时间关系。
DOI：
10.1006/excr.1996.3401
发表时间：
1997
期刊：
Experimental cell research.
影响因子：
--
作者：
Wolf,CM;Reynolds,JE;Morana,SJ;Eastman,A
通讯作者：
Eastman,A
影响因子：
3.1
作者：
Y. Ohoka;Yuji Nakai;M. Mukai;Makoto Iwata
通讯作者：
Y. Ohoka;Yuji Nakai;M. Mukai;Makoto Iwata
检测与细胞凋亡相关的 DNA 片段、核酸内切酶以及细胞内 pH 和 Ca2。
影响因子：
--
作者：
Alan Eastman
通讯作者：
Alan Eastman
影响因子：
3.9
作者：
BARRY, MA;EASTMAN, A
通讯作者：
EASTMAN, A
蛋白磷酸酶抑制剂对三叉神经神经瘤细胞细胞变圆和细胞凋亡的调节。
影响因子：
2
作者：
K. Marushige;Y. Marushige
通讯作者：
Y. Marushige