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• W2067092931 abstract "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. FASEB J. 27, 208–221 (2013). www.fasebj.org" @default.
• W2067092931 created "2016-06-24" @default.
• W2067092931 creator A5049410101 @default.
• W2067092931 creator A5069953764 @default.
• W2067092931 date "2012-10-04" @default.
• W2067092931 modified "2023-09-26" @default.
• W2067092931 title "Regulation of RCAN1 translation and its role in oxidative stress‐induced apoptosis" @default.
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• W2067092931 doi "https://doi.org/10.1096/fj.12-213124" @default.
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