RCAN1 Overexpression Exacerbates Calcium Overloading-Induced Neuronal Apoptosis

被引：36
作者：
Sun, Xiulian [1 ,4 ]
Wu, Yili [2 ,3 ,4 ]
Herculano, Bruno [4 ]
Song, Weihong [2 ,3 ,4 ]
机构：
[1] Shandong Univ, Qilu Hosp, Jinan 250100, Peoples R China
[2] Chongqing Med Univ, Childrens Hosp, Chongqing City Key Lab Translat Med Res Cognit De, Chongqing, Peoples R China
[3] Chongqing Med Univ, Childrens Hosp, Minist Educ, Key Lab Child Dev & Disorders, Chongqing, Peoples R China
[4] Univ British Columbia, Grad Program Neurosci, Brain Res Ctr, Dept Psychiat,Townsend Family Labs, Vancouver, BC V5Z 1M9, Canada
来源：
PLOS ONE | 2014年 / 9卷 / 04期
基金：
中国国家自然科学基金; 加拿大健康研究院;
关键词：
DOWN-SYNDROME; ALZHEIMERS-DISEASE; TRANSCRIPTION FACTORS; INHIBITS CALCINEURIN; OXIDATIVE STRESS; PROTEIN; DSCR1; EXPRESSION; GENE; PHOSPHORYLATION;
D O I：
10.1371/journal.pone.0095471
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
Down Syndrome (DS) patients develop characteristic Alzheimer's Disease (AD) neuropathology after their middle age. Prominent neuronal loss has been observed in the cortical regions of AD brains. However, the underlying mechanism leading to this neuronal loss in both DS and AD remains to be elucidated. Calcium overloading and oxidative stress have been implicated in AD pathogenesis. Two major isoforms of regulator of calcineurin 1 (RCAN1), RCAN1.1 and RCAN1.4, are detected in human brains. In this report we defined the transcriptional regulation of RCAN1.1 and RCAN1.4 by two alternative promoters. Calcium overloading upregulated RCAN1.4 expression by activating RCAN1.4 promoter through calcineurin-NFAT signaling pathway, thus forming a negative feedback loop in isoform 4 regulation. Furthermore, RCAN1.4 overexpression exacerbated calcium overloading-induced neuronal apoptosis, which was mediated by caspase-3 apoptotic pathway. Our results suggest that downregulating RCAN1.4 expression in neurons could be beneficial to AD patients.
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页数：8
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