| Regulation of RCAN1 translation and its role in oxidative stress-induced apoptosis. | |
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MedLine Citation:
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PMID: 23038757 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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Yili Wu; Weihong Song |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-10-4 |
Journal Detail:
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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:
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Created Date: 2012-10-5 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8804484 Medline TA: FASEB J Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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*Chongqing City Key Lab of Translational Medical Research in Cognitive Development and Learning and Memory Disorders and. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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