title: CREB-mediated Bcl-2 expression contributes to RCAN1 protection from hydrogen peroxide-induced neuronal death.
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.
authors.affiliation: Department of Molecular Bioscience, College of Biomedical Science, Institute of Bioscience & Biotechnology, Kangwon National University, Hyoja-dong, Chuncheon 200-701, Republic of Korea.
authors.forename: Seon Sook
authors.initials: SS
authors.lastname: Kim
authors.forename: Shin Ah
authors.initials: SA
authors.lastname: Jang
authors.forename: Su Ryeon
authors.initials: SR
authors.lastname: Seo
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D019610:Cytoprotection / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D016716:PC12 Cells; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051381:Rats; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D047908:Intracellular Signaling Peptides and Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C548050:RCAN1 protein, rat; D018808:Transcription Factor AP-1; D006861:Hydrogen Peroxide; D020928:Mitogen-Activated Protein Kinases