Research Papers:

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

Li Mao, Mei-Ling Zuo, Guo-Huang Hu, Xiao-Ming Duan and Zhong-Bao Yang _

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Oncotarget. 2017; 8:99681-99692. https://doi.org/10.18632/oncotarget.21129

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Li Mao1,*, Mei-Ling Zuo2,*, Guo-Huang Hu2, Xiao-Ming Duan2 and Zhong-Bao Yang2

1ChangSha Health Vocational College, Changsha 410100, China

2The Affiliated ChangSha Hospital of HuNan Normal University, Changsha 410006, China

*These authors contributed equally to this work

Correspondence to:

Zhong-Bao Yang, email: [email protected]

Guo-Huang Hu, email: [email protected]

Xiao-Ming Duan, email: [email protected]

Keywords: cerebral ischemia/reperfusion injury, miR-193, ALDH2, tyrosine hydroxylase (TH)

Abbreviations: I/R: cerebral ischemia/reperfusion injury, 4-HNE: 4-Hydroxynonenal, MDA: Malondialdehyde, TH: tyrosine hydroxylase

Received: April 03, 2017     Accepted: September 04, 2017     Published: September 21, 2017


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.

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