MicroRNA-214 participates in the neuroprotective effect of Resveratrol via inhibiting α-synuclein expression in MPTP-induced Parkinson's disease mouse.
OBJECTIVE
MicroRNAs (miRNAs) have been reported to be involved in degenerative disorders including Parkinson's disease (PD). α-synuclein expression is strong associated with the pathogenesis of PD. In the present study, we investigated whether the regulation of α-synuclein expression by miR-214 is the potential mechanism underlying the neuroprotective effect of Resveratrol.


METHODS
The PD mouse model was established with the injection of MPTP (1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and the human neuroblastoma cell line, SH-SY5Y, was administrated with MPP+.


RESULTS
The midbrain of PD mice and MPP+ treated SH-SY5Y cells had the lower expression levels of miR-214 and higher mRNA and protein expression of α-synuclein, which were reversed by Resveratrol administration. MiR-214 mimic down-regulated expression of α-synuclein and its 3'-UTR activity, while the levels were up-regulated by miR-214 inhibitor. In addition, the cell viability, elevated by Resveratrol, was also decreased by miR-214 inhibitor or overexpressed α-synuclein. In vivo, miR-214 inhibitor down-regulated TH+ cells of ipsilateral and up-regulated α-synuclein expression compared with the group treated with Resveratrol.


CONCLUSIONS
The loss of miR-214 in PD resulted in the increase of α-synuclein expression, which was the potential mechanism underlying the neuroprotective effects of Resveratrol.
Department of Internal Neurology, Huaihe Hospital of Henan University, Kaifeng 475000, China. Electronic address: wzhdyl0526@163.com.
Zhao-Hui
ZH
Wang
Department of Internal Neurology, Huaihe Hospital of Henan University, Kaifeng 475000, China.
Jian-Lei
JL
Zhang
Department of Ultrasound, Kaifeng Maternity hospital, Kaifeng 475000, China.
Yan-Li
YL
Duan
Department of Internal Neurology, Huaihe Hospital of Henan University, Kaifeng 475000, China.
Qi-Shun
QS
Zhang
Department of Internal Neurology, Huaihe Hospital of Henan University, Kaifeng 475000, China.
Guo-Fei
GF
Li
Department of Internal Neurology, Huaihe Hospital of Henan University, Kaifeng 475000, China.
Dong-Lin
DL
Zheng
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000008:administration & dosage; D000818:Animals; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics*; D009447:Neuroblastoma / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020734:Parkinsonian Disorders / Q000188:drug therapy*; D012333:RNA, Messenger / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects; D051844:alpha-Synuclein / Q000235:genetics
D035683:MicroRNAs; C534781:Mirn214 microRNA, mouse; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D013267:Stilbenes; D051844:alpha-Synuclein; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000077185:Resveratrol
Parkinson’s disease; Resveratrol; miR-214; α-Synuclein