Abstract:
: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 (RCAN1(ox)) 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 (PC12(RCAN1)). Similar to RCAN1(ox) neurons, PC12(RCAN1) 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.
journal_name
Oxid Med Cell Longevjournal_title
Oxidative medicine and cellular longevityauthors
Peiris H,Dubach D,Jessup CF,Unterweger P,Raghupathi R,Muyderman H,Zanin MP,Mackenzie K,Pritchard MA,Keating DJdoi
10.1155/2014/520316subject
Has Abstractpub_date
2014-01-01 00:00:00pages
520316eissn
1942-0900issn
1942-0994journal_volume
2014pub_type
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journal_title:Oxidative medicine and cellular longevity
pub_type: 杂志文章,评审
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journal_title:Oxidative medicine and cellular longevity
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journal_title:Oxidative medicine and cellular longevity
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journal_title:Oxidative medicine and cellular longevity
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journal_title:Oxidative medicine and cellular longevity
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journal_title:Oxidative medicine and cellular longevity
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journal_title:Oxidative medicine and cellular longevity
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journal_title:Oxidative medicine and cellular longevity
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journal_title:Oxidative medicine and cellular longevity
pub_type: 杂志文章
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更新日期:2015-01-01 00:00:00
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journal_title:Oxidative medicine and cellular longevity
pub_type: 杂志文章
doi:10.1155/2018/7514383
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journal_title:Oxidative medicine and cellular longevity
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journal_title:Oxidative medicine and cellular longevity
pub_type: 杂志文章
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更新日期:2011-01-01 00:00:00
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journal_title:Oxidative medicine and cellular longevity
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journal_title:Oxidative medicine and cellular longevity
pub_type: 杂志文章
doi:10.4161/oxim.2.3.8804
更新日期:2009-07-01 00:00:00
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journal_title:Oxidative medicine and cellular longevity
pub_type: 杂志文章
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更新日期:2014-01-01 00:00:00
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journal_title:Oxidative medicine and cellular longevity
pub_type: 已发布勘误
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journal_title:Oxidative medicine and cellular longevity
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journal_title:Oxidative medicine and cellular longevity
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journal_title:Oxidative medicine and cellular longevity
pub_type: 杂志文章
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