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[溶酶体膜通透性作为凋亡诱导因子]

[Lysosomal membrane permeabilization as apoptogenic factor].

作者信息

Pupyshev A B

出版信息

Tsitologiia. 2011;53(4):313-24.

Abstract

Lysosomal membrane labilizing agents (incl. proapoptotic proteins of Bcl-2 family, LAPF, p53), estimation of lysosomal membrane permeabilization in living cells, the new data on differential permeabilization of lysosomal membranes, membrane stabilizing factors (incl. Hsp70), relations between lysosomal membrane damage, and initiation of apoptosis were considered. Signal effect of lysosomal membrane permeabilization is caused preferentially by release of cathepsin B and D in cytosol. Subsequent numerous pathways of apoptogenic signalization include proteolytic attack/activation on signal cytosolic proteins, mitochondria, procaspases, cell nuclei. The mainstream of the cell damage is connected with activation pf proapoptotic Bid and Bax, leading to permeabilization of the outer mitochondrial membrane, release of cytochrome c into cytosol and activation of caspase cascade. Translocation of the lysosoma enzymes in cytosol is capable to induce both the caspase-dependent and caspase-independent paths of apoptosis.

摘要

溶酶体膜不稳定剂(包括Bcl-2家族的促凋亡蛋白、LAPF、p53)、活细胞中溶酶体膜通透性的评估、溶酶体膜差异通透性的新数据、膜稳定因子(包括Hsp70)、溶酶体膜损伤与细胞凋亡起始之间的关系均被考虑在内。溶酶体膜通透性的信号效应主要由组织蛋白酶B和D释放到细胞质中引起。随后众多的凋亡信号通路包括对细胞质信号蛋白、线粒体、procaspases、细胞核的蛋白水解攻击/激活。细胞损伤的主流与促凋亡Bid和Bax的激活有关,导致线粒体外膜通透性增加、细胞色素c释放到细胞质中以及caspase级联反应的激活。溶酶体酶在细胞质中的易位能够诱导caspase依赖性和caspase非依赖性的凋亡途径。

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