RCAN1 regulates mitochondrial function and increases susceptibility to oxidative stress in mammalian cells.
RCAN1 regulates mitochondrial function and increases susceptibility to oxidative stress in mammalian cells.
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RCAN1 调节线粒体功能并增加哺乳动物细胞对氧化应激的敏感性。
DOI：
10.1155/2014/520316
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发表时间：
2014
影响因子：
--
通讯作者：
Keating DJ
中科院分区：
文献类型：
--
作者：
Peiris H;Dubach D;Jessup CF;Unterweger P;Raghupathi R;Muyderman H;Zanin MP;Mackenzie K;Pritchard MA;Keating DJ
线粒体是细胞能量产生和活性氧（ROS）积累的主要场所。升高的ROS水平对正常细胞功能是有害的，并且与神经退行性疾病如唐氏综合征（DS）和阿尔茨海默病（AD）的发病机制有关。RCAN1在脑中大量表达，并且在DS和AD患者的脑中过表达。来自非哺乳动物物种的数据表明，RCAN1表达增加导致线粒体功能改变，RCAN1本身可能调节神经元ROS的产生。在这项研究中，我们利用过表达RCAN1（RCAN1ox）的小鼠，并证明这些小鼠的神经元对氧化应激的敏感性增加。来自这些小鼠的线粒体更多且更小，指示线粒体功能障碍，并且线粒体膜电位在氧化应激条件下改变。我们还产生了过表达RCAN1的PC12细胞系（PC12RCAN1）。与RCAN1ox神经元类似，PC12 RCAN1细胞对氧化应激的敏感性增加，并产生更多的线粒体ROS。这项研究表明，增加RCAN1表达改变线粒体功能，增加神经元对哺乳动物细胞氧化应激的易感性。这些发现进一步有助于我们了解RCAN1及其在神经退行性疾病（如AD和DS）发病机制中的潜在作用。
Mitochondria are the primary site of cellular energy generation and reactive oxygen species (ROS) accumulation. Elevated ROS levels are detrimental to normal cell function and have been linked to the pathogenesis of neurodegenerative disorders such as Down's syndrome (DS) and Alzheimer's disease (AD). RCAN1 is abundantly expressed in the brain and overexpressed in brain of DS and AD patients. Data from nonmammalian species indicates that increased RCAN1 expression results in altered mitochondrial function and that RCAN1 may itself regulate neuronal ROS production. In this study, we have utilized mice overexpressing RCAN1 (RCAN1ox) and demonstrate an increased susceptibility of neurons from these mice to oxidative stress. Mitochondria from these mice are more numerous and smaller, indicative of mitochondrial dysfunction, and mitochondrial membrane potential is altered under conditions of oxidative stress. We also generated a PC12 cell line overexpressing RCAN1 (PC12RCAN1). Similar to RCAN1ox neurons, PC12RCAN1 cells have an increased susceptibility to oxidative stress and produce more mitochondrial ROS. This study demonstrates that increasing RCAN1 expression alters mitochondrial function and increases the susceptibility of neurons to oxidative stress in mammalian cells. These findings further contribute to our understanding of RCAN1 and its potential role in the pathogenesis of neurodegenerative disorders such as AD and DS.
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影响因子：
4.8
作者：
Ermak, Gennady;Sojitra, Sonal;Davies, Kelvin J. A.
通讯作者：
Davies, Kelvin J. A.
影响因子：
4.8
作者：
Asai, A;Qiu, JH;Kirino, T
通讯作者：
Kirino, T
影响因子：
4.8
作者：
Ermak, G;Morgan, TE;Davies, KJA
通讯作者：
Davies, KJA
影响因子：
5.4
作者：
Harris, Cathryn D.;Ermak, Gennady;Davies, Kelvin J. A.
通讯作者：
Davies, Kelvin J. A.
影响因子：
5.3
作者：
Cho, Kyung-Ok;Kim, Young Sun;Kim, Seong Yun
通讯作者：
Kim, Seong Yun