Overexpressed cyclophilin B suppresses apoptosis associated with ROS and Ca2+ homeostasis after ER stress.
Overexpressed cyclophilin B suppresses apoptosis associated with ROS and Ca2+ homeostasis after ER stress.
复制标题
过表达的环糖蛋白B抑制与ROS和Ca2+稳态相关的凋亡。
DOI：
10.1242/jcs.028654
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发表时间：
2008-11-01
影响因子：
4
通讯作者：
Kim SS
中科院分区：
文献类型：
--
作者：
Kim J;Choi TG;Ding Y;Kim Y;Ha KS;Lee KH;Kang I;Ha J;Kaufman RJ;Lee J;Choe W;Kim SS
错误折叠蛋白在内质网（ER）中的长期积累导致ER应激介导的细胞凋亡。亲环素是蛋白质伴侣，通过其肽基脯氨酰顺反异构酶（PPI酶）活性加速蛋白质折叠速率。在这项研究中，我们证明，ER应激激活ER定位亲环素B（CypB）基因的表达，通过一种新的ER应激反应元件。野生型CypB的过表达减弱了ER应激诱导的细胞死亡，而异构酶活性缺陷突变体CypB/R62 A的过表达不仅增加了ER和ROS产生的Ca 2+渗漏，而且降低了线粒体膜电位，导致暴露于ER应激诱导剂后细胞死亡。siRNA介导的CypB表达抑制使细胞更容易受到ER应激的影响。最后，CypB与ER应激相关的伴侣Bip和Grp 94相互作用。综上所述，我们得出结论，CypB通过其PPIase活性在保护细胞免受ER应激方面发挥关键作用。
Prolonged accumulation of misfolded proteins in the endoplasmic reticulum (ER) results in ER stress-mediated apoptosis. Cyclophilins are protein chaperones that accelerate the rate of protein folding through their peptidyl-prolyl cis-trans isomerase (PPIase) activity. In this study, we demonstrated that ER stress activates the expression of the ER-localized cyclophilin B (CypB) gene through a novel ER stress response element. Overexpression of wild-type CypB attenuated ER stress-induced cell death, whereas overexpression of an isomerase activity-defective mutant, CypB/R62A, not only increased Ca2+ leakage from the ER and ROS generation, but also decreased mitochondrial membrane potential, resulting in cell death following exposure to ER stress-inducing agents. siRNA-mediated inhibition of CypB expression rendered cells more vulnerable to ER stress. Finally, CypB interacted with the ER stress-related chaperones, Bip and Grp94. Taken together, we concluded that CypB performs a crucial function in protecting cells against ER stress via its PPIase activity.
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影响因子：
7.8
作者：
Hitomi, Junichi;Katayama, Taiichi;Eguchi, Yutaka;Kudo, Takashi;Taniguchi, Manabu;Koyama, Yoshihisa;Manabe, Takayuki;Yamagishi, Satoru;Bando, Yoshio;Imaizumi, Kazunori;Tsujimoto, Yoshihide;Tohyama, Masaya
通讯作者：
Tohyama, Masaya
影响因子：
11.2
作者：
Choi, Kyu Jin;Piao, Yu Ji;Kim, Sung Soo
通讯作者：
Kim, Sung Soo
影响因子：
16
作者：
Chae, HJ;Kim, HR;Reed, JC
通讯作者：
Reed, JC
DOI：
10.1111/j.1749-6632.2002.tb04837.x
发表时间：
2002-01-01
期刊：
ALZHEIMER'S DISEASE: VASCULAR ETIOLOGY AND PATHOLOGY
影响因子：
--
作者：
Kudo, T;Katayama, T;Takeda, M
通讯作者：
Takeda, M
影响因子：
64.8
作者：
Baines, CP;Kaiser, RA;Molkentin, JD
通讯作者：
Molkentin, JD