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.