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MicroRNA-7 inhibits neuronal apoptosis in a cellular Parkinson's disease model by targeting Bax and Sirt2.

Shize LiDepartment of Neurology, The Second Affiliated Hospital of Zhengzhou University Zhengzhou 450014, ChinaXuecheng LvDepartment of Pharmacy, The First People's Hospital of Shangqiu 476100, Henan, ChinaKaihua ZhaiDepartment of Neurology, The Second Affiliated Hospital of Zhengzhou University Zhengzhou 450014, ChinaRuyan XuDepartment of Neurology, Zhengzhou Central Hospital Affiliated to Zhengzhou University Zhengzhou 450007, ChinaYong ZhangDepartment of Neurology, Zhengzhou Central Hospital Affiliated to Zhengzhou University Zhengzhou 450007, ChinaSongyao ZhaoDepartment of Neurology, Zhengzhou Central Hospital Affiliated to Zhengzhou University Zhengzhou 450007, ChinaXiaoming QinDepartment of Neurology, Zhengzhou Central Hospital Affiliated to Zhengzhou University Zhengzhou 450007, ChinaLiujie YinDepartment of Neurology, Zhengzhou Central Hospital Affiliated to Zhengzhou University Zhengzhou 450007, ChinaJiyu LouDepartment of Neurology, The Second Affiliated Hospital of Zhengzhou University Zhengzhou 450014, China
2016en
ABI

Аннотация

Parkinson's disease (PD) is the second most common age-related neurodegenerative disease. MicroRNA-7 (miR-7) displays neuroprotective properties against PD. However, the biological roles of miR-7 and its underlying molecular mechanisms in PD remain unclear. We demonstrated herein that 1-methyl-4-phenylpyridinium ion (MPP(+)) confers toxic effects on dopaminergic neuron in a dose-dependent manner in a cellular PD model, although this phenomenon is attenuated by miR-7 treatment. Introduction of miR-7 inhibits MPP(+)-induced neuronal apoptosis as reflected by the reduced terminal transferase-mediated dUTP nick end labeling-positive rate, mitochondrial permeability potential, caspase 3 activity, and nucleosomal enrichment factor. Bax and sirtuin 2 (Sirt2) are the direct targets of miR-7. Moreover, the effects of miR-7 were counteracted by Bax and Sirt2 overexpression, respectively. The altered molecular expressions downstream of Bax and Sirt2 are also involved in miR-7 regulation of the MPP(+)-triggered neuronal apoptosis. These findings have implications on the potential application of miR-7 in PD treatment.

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