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

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.

Citing Articles

The Role of microRNAs in Epigenetic Regulation of Signaling Pathways in Neurological Pathologies.

Tregub P, Ibrahimli I, Averchuk A, Salmina A, Litvitskiy P, Manasova Z Int J Mol Sci. 2023; 24(16).

PMID: 37629078 PMC: 10454825. DOI: 10.3390/ijms241612899.

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