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CREB‐mediated Bcl‐2 expression contributes to RCAN1 protection from hydrogen peroxide‐induced neuronal death
Author(s) -
Kim Seon Sook,
Jang Shin Ah,
Seo Su Ryeon
Publication year - 2013
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.24452
Subject(s) - creb , gene knockdown , microbiology and biotechnology , reactive oxygen species , phosphorylation , apoptosis , chemistry , protein kinase a , kinase , biology , transcription factor , biochemistry , gene
Abstract Regulator of calcineurin 1 (RCAN1) is located on the Down syndrome critical region (DSCR) locus in human chromosome 21. In this study, we investigated the functional role of RCAN1 in the reactive oxygen species (ROS)‐mediated neuronal death signaling. We found that RCAN1 was able to protect the cells from H 2 O 2 ‐induced cytotoxicity. The expression of RCAN1 caused an inhibition of the H 2 O 2 ‐induced activation of mitogen‐activated protein kinases (MAPKs) and AP‐1. In contrast, RCAN1 significantly enhanced the activity of cAMP response element‐binding protein (CREB). Furthermore, RCAN1 induced the expression of the CREB target gene, Bcl‐2. Consistently, knockdown of endogenous RCAN1 using shRNA down regulated the phosphorylation of CREB and the expression of Bcl‐2, which protects the cells from H 2 O 2 ‐induced cytotoxicity. Our data provide a new mechanism for the cytoprotective function of RCAN1 in response to oxidant‐induced apoptosis. J. Cell. Biochem. 114: 1115–1123, 2013. © 2012 Wiley Periodicals, Inc.