OL-FS13 Alleviates Cerebral Ischemia-reperfusion Injury by Inhibiting miR-21-3p Expression

Author:

Liu Naixin1,Fan Yan1,Li Yilin1,Zhang Yingxuan1,Li Jiayi1,Wang Yinglei1,Wang Zhuo1,Liu Yixiang2,Li Yuansheng1,Kang Zijian1,Peng Ying1,Ru Zeqiong1,Yang Meifeng1,Feng Chengan1,Wang Ying2,Yang Xinwang1

Affiliation:

1. Department of Anatomy and Histology & Embryology, Faculty of Basic Medical Science, Kunming Medical University, Kunming, 650500, Yunnan, China

2. Key Laboratory of Chemistry in Ethnic Medicinal Resources & Key Laboratory of Natural Products Synthetic Biology of Ethnic Medicinal Endophytes, School of Ethnic Medicine, Yunnan Minzu University, State Ethnic Affairs Commission & Ministry of Education, Kunming, Yunnan, 650504, China

Abstract

Background: OL-FS13, a neuroprotective peptide derived from Odorrana livida, can alleviate cerebral ischemia-reperfusion (CI/R) injury, although the specific underlying mechanism remains to be further explored. Objective: The effect of miR-21-3p on the neural-protective effects of OL-FS13 was examined. Methods: In this study, the multiple genome sequencing analysis, double luciferase experiment, RT-qPCR, and Western blotting were used to explore the mechanism of OL-FS13. Results: Showed that over-expression of miR-21-3p against the protective effects of OL-FS13 on oxygen- glucose deprivation/re-oxygenation (OGD/R)-damaged pheochromocytoma (PC12) cells and in CI/R-injured rats. miR-21-3p was then found to target calcium/calmodulin-dependent protein kinase 2 (CAMKK2), and its overexpression inhibited the expression of CAMKK2 and phosphorylation of its downstream adenosine 5’-monophosphate (AMP)-activated protein kinase (AMPK), thereby inhibiting the therapeutic effects of OL-FS13 on OGD/R and CI/R. Inhibition of CAMKK2 also antagonized up-regulated of nuclear factor erythroid 2-related factor 2 (Nrf-2) by OL-FS13, thereby abolishing the antioxidant activity of the peptide. Conclusion: Our results showed that OL-FS13 alleviated OGD/R and CI/R by inhibiting miR-21-3p to activate the CAMKK2/AMPK/Nrf-2 axis.

Funder

Yunnan Applied Basic Research Project-Kunming Medical University Union Foundation

National Natural Science Foundation of China

Yunnan Applied Basic Research Project Foundation

Publisher

Bentham Science Publishers Ltd.

Subject

Pharmacology (medical),Psychiatry and Mental health,Neurology (clinical),Neurology,Pharmacology,General Medicine

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