IDH1 Associated with Neuronal Apoptosis in Adult Rats Brain Following Intracerebral Hemorrhage

Chen, Xing; Wang, Hongmei; Yu, Weibing; Chen, Fen; Wang, Guiyun; Shi, Jiajia; Zhou, Chunying

doi:10.1007/s10571-016-0421-9

Original Research
Published: 27 August 2016

IDH1 Associated with Neuronal Apoptosis in Adult Rats Brain Following Intracerebral Hemorrhage

Xing Chen^1,3,
Hongmei Wang^2,3,
Weibing Yu^1,3,
Fen Chen^1,3,
Guiyun Wang^1,3,
Jiajia Shi^1,3 &
Chunying Zhou^1,3

Cellular and Molecular Neurobiology volume 37, pages 831–841 (2017)Cite this article

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Abstract

Isocitrate dehydrogenase 1 (IDH1), one member of the IDH family can convert isocitrate to α-ketoglutarate (α-KG) via oxidative decarboxylation. IDH1 and IDH2 mutations have been identified in multiple tumor types and the mutations confer neomorphic activity in the mutant protein, resulting in the conversion of α-KG to the oncometabolite, D-2-hydroxyglutarate (2-HG). The subsequent accumulation of 2-HG results in epigenetic dysregulation via inhibition of α-KG-dependent histone and DNA demethylase. And the glutamate levels are reduced in IDH mutant cells compared to wild-type. We have known that diffuse gliomas contain a high frequency of mutations in the IDH1 gene. However, the expression of IDH1 and its roles in Intracranial hemorrhage (ICH) remain largely unknown. We observed increased expression of IDH1 in neurons after intracerebral hemorrhage. Up-regulation of IDH1 was found to be accompanied by the increased expression of active caspase-3 and pro-apoptotic Bcl-2-associated X protein and decreased expression of anti-apoptotic protein B cell lymphoma-2 in vivo and vitro studies. So we hypothesized that IDH1 was involved in the regulation of neuronal apoptosis. The present research for the first time detected the expression and variation of IDH1 surrounding the hematoma, and all data proved the involvement of IDH1 in neuronal apoptosis following ICH.

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Affiliations

Department of Neurology, Nantong University Affiliated Mental Health Center, Nantong, 226001, Jiangsu Province, People’s Republic of China
Xing Chen, Weibing Yu, Fen Chen, Guiyun Wang, Jiajia Shi & Chunying Zhou
Department of Neurology, Affiliated Hospital of Nantong University, Nantong, 226000, Jiangsu, People’s Republic of China
Hongmei Wang
Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001, Jiangsu Province, People’s Republic of China
Xing Chen, Hongmei Wang, Weibing Yu, Fen Chen, Guiyun Wang, Jiajia Shi & Chunying Zhou

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Xing Chen
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Hongmei Wang
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Weibing Yu
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Fen Chen
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Guiyun Wang
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Jiajia Shi
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Chunying Zhou
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Correspondence to Chunying Zhou.

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Xing Chen and Hongmei Wang have contributed equally to this work.

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Chen, X., Wang, H., Yu, W. et al. IDH1 Associated with Neuronal Apoptosis in Adult Rats Brain Following Intracerebral Hemorrhage. Cell Mol Neurobiol 37, 831–841 (2017). https://doi.org/10.1007/s10571-016-0421-9

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Received: 08 June 2016
Accepted: 17 August 2016
Published: 27 August 2016
Issue Date: July 2017
DOI: https://doi.org/10.1007/s10571-016-0421-9

Keywords

ICH
IDH1
Neuron
Apoptosis
Active caspase-3