Document Detail


Regulation of RCAN1 translation and its role in oxidative stress-induced apoptosis.
MedLine Citation:
PMID:  23038757     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Abnormal expression of regulator of calcineurin 1 (RCAN1) has been implicated in Alzheimer's disease (AD) and Down's syndrome (DS). There are two major isoforms of RCAN1, isoforms 1 and 4. RCAN1 isoform 1 is predominantly expressed in the brain, particularly in neurons. In this report, we showed that there are two translation start codons in RCAN1 exon 1 serving as a functional translation initiation site to generate a longer 41-kDa isoform 1 (RCAN1.1L) and a shorter 31-kDa isoform 1 (RCAN1.1S). The first translation initiation site has higher translation efficiency than the downstream second one, and the translation initiation of two AUG sites is by a Cap-dependent mechanism. Short-term expression of RCAN1.1L protected SH-SY5Y cells from oxidative stress-induced apoptosis by inhibiting caspase-3 activation. However, long-term accumulation of RCAN1.1L in SH-SY5Y cells promoted oxidative stress-induced apoptosis via caspase-3 activation, and terminal deoxynucleotidyl transferase dUTP nick end labeling assay showed that the apoptosis ratio was increased to 499.03 ± 47.56% in SH-1.1L cells compared with 283.93 ± 28.66% in control cells. Furthermore, we found that RCAN1.1L is significantly elevated in the AD brains and patients with DS. RCAN1.1S is expressed at a low level in both human cells and brain tissues. Our results defined the regulatory mechanism underlying RCAN1 expression and the roles of RCAN1.1 in oxidative stress-induced neurodegeneration in AD and DS pathogenesis.-Wu, Y., Song, W. Regulation of RCAN1 translation and its role in oxidative stress-induced apoptosis.
Authors:
Yili Wu; Weihong Song
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-4
Journal Detail:
Title:  FASEB journal : official publication of the Federation of American Societies for Experimental Biology     Volume:  -     ISSN:  1530-6860     ISO Abbreviation:  FASEB J.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-5     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8804484     Medline TA:  FASEB J     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
*Chongqing City Key Lab of Translational Medical Research in Cognitive Development and Learning and Memory Disorders and.
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