Overexpressed Cyclophilin B Suppresses Apoptosis Associated with ROS and Ca2+ Homeostasis After ER Stress

Overview

Journal J Cell Sci

Specialty Cell Biology

Date 2008 Oct 24

PMID 18946027

Citations 46

Authors

Jinhwan Kim

Tae Gyu Choi

Yan Ding

Yeonghwan Kim

Kwon Soo Ha

Kyung Ho Lee

Insug Kang

Joohun Ha

Randal J Kaufman

Jinhwa Lee

Wonchae Choe

Sung Soo Kim

Affiliations

Soon will be listed here.

Abstract

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 Ca(2+) 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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