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Mir-193 targets ALDH2 and contributes to toxic aldehyde accumulation and tyrosine hydroxylase dysfunction in cerebral ischemia/reperfusion injury.

ABSTRACT: MicroRNAs (miRNAs, miR) play a fundamental role in cerebral ischemia/reperfusion (I/R) injury. However, the role of miRNAs in toxic aldehyde and tyrosine accumulation is not fully elucidated. We constructed a cerebral I/R rat model and found that overexpression of miR-193 was associated with the accumulation of 4-Hydroxynonenal (4-HNE), Malondialdehyde (MDA), and tyrosine, and with the decrease of aldehyde dehydrogenase (ALDH2), tyrosine hydroxylase (TH), and dopamine. To unveil the molecular mechanism of the miR-193-mediated phenotype in I/R injury as described above, we performed bioinformatic analysis and found that ALDH2 was a potential target of miR-193. Through in vitro experiments (such as miR-193 mimic/inhibitor transfection, luciferase reporter gene plasmid transfection, and 4-HNE exposure) and in vivo infusion of miR-193 agomir, we demonstrated that miR-193 directly suppressed the expression of ALDH2 and led to toxic aldehyde accumulation, resulting in dysfunction of tyrosine hydroxylase. The present study suggests that the overexpression of miR-193 in a rat model exacerbated brain injury due to the following sequential process: targeted suppression of ALDH2, aldehyde accumulation, and tyrosine hydroxylase dysfunction, leading to tyrosine accumulation and insufficiency of dopamine synthesis.

SUBMITTER: Mao L

PROVIDER: S-EPMC5725124 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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mir-193 targets ALDH2 and contributes to toxic aldehyde accumulation and tyrosine hydroxylase dysfunction in cerebral ischemia/reperfusion injury.

Mao Li L Zuo Mei-Ling ML Hu Guo-Huang GH Duan Xiao-Ming XM Yang Zhong-Bao ZB

Oncotarget 20170921 59

MicroRNAs (miRNAs, miR) play a fundamental role in cerebral ischemia/reperfusion (I/R) injury. However, the role of miRNAs in toxic aldehyde and tyrosine accumulation is not fully elucidated. We constructed a cerebral I/R rat model and found that overexpression of miR-193 was associated with the accumulation of 4-Hydroxynonenal (4-HNE), Malondialdehyde (MDA), and tyrosine, and with the decrease of aldehyde dehydrogenase (ALDH2), tyrosine hydroxylase (TH), and dopamine. To unveil the molecular me ...[more]

PMID: 29245933

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Dataset Information

Mir-193 targets ALDH2 and contributes to toxic aldehyde accumulation and tyrosine hydroxylase dysfunction in cerebral ischemia/reperfusion injury.

Publications

mir-193 targets ALDH2 and contributes to toxic aldehyde accumulation and tyrosine hydroxylase dysfunction in cerebral ischemia/reperfusion injury.

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