Overexpressed cyclophilin B suppresses apoptosis associated with ROS and Ca2+ homeostasis after ER stress

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 activitydefective 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. siRNAmediated 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. Supplementary material available online at

Participation of endoplasmic reticulum stress in the pathogenesis of spontaneous glomerulosclerosis–Role of intra-renal angiotensin system

“…In addition, the observed reduction of cyclophilin B, which facilitates protein folding via its peptidyl-prolyl isomerase activity, further contributes to the failure of the ER adaptive response in this model. 29 In an earlier study, we found marked reduction of nuclear translocation of Nrf2 and downregulation of the antioxidant and cytoprotective byproducts of its target genes in the kidneys of Imai rats. 22 In confirmation of the latter study, we found marked reduction of nuclear Nrf2 content in the untreated Imai rat kidneys.…”

Cyclophilin B is involved in p300-mediated degradation of CHOP in tumor cell adaptation to hypoxia

“…GST-CypB and CypB series region reporter plasmids have been described previously. 10 The active-ATF6 expression vector was kindly provided by Dr. Kyung Ho Lee (Konkuk University, Seoul, Korea). The human CHOP promoter reporter constructs were kindly provided by Dr. P Fafournoux (Unité Nutrition Humaine, INRA de Theix, Champanelle, France).…”

“…Recently, we showed that Cyclophilin B (CypB) blocks Ca 2 þ leakage from the ER to cytosol against the ER stress-inducing drug, thapsigargin (Ca 2 þ ATPase (SERCA) blocker), and ultimately prevents cell death in response to ER stress. 10 However, the exact molecular mechanism by which CypB protects against ER stress is still elusive.…”

Mitochondrial H2O2 generated from electron transport chain complex I stimulates muscle differentiation

“…Conventional ChIP was conducted as described previously [46], except that cross-linked H9c2 chromatin was subjected to immunoprecipitation with an antibody against the p65 subunit of NF-κB. The MnSOD promoter containing a binding site of NF-κB was amplified using the following primers: forward, 5′-CCCTCCTGGTAACAGTGTTAG-3′ and reverse, 5′-GCCTACTAAGGATGACTGGG-3′.…”