Department of Anatomy and Histology & Embryology, Faculty of Basic Medical Science, Kunming Medical University, Kunming, 650500, Yunnan, China.
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.
Curr Neuropharmacol. 2023;21(12):2550-2562. doi: 10.2174/1570159X21666230502111013.
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.
The effect of miR-21-3p on the neural-protective effects of OL-FS13 was examined.
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.
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.
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.
OL-FS13 是一种从中国林蛙中提取的神经保护肽，可减轻脑缺血再灌注（CI/R）损伤，但其具体作用机制仍需进一步探讨。
研究 miR-21-3p 对 OL-FS13 的神经保护作用的影响。
本研究采用多种基因组测序分析、双荧光素酶实验、RT-qPCR 和 Western blot 等方法探讨 OL-FS13 的作用机制。
结果表明，miR-21-3p 的过表达可拮抗 OL-FS13 对氧葡萄糖剥夺/复氧（OGD/R）损伤的嗜铬细胞瘤（PC12）细胞和 CI/R 损伤大鼠的保护作用。miR-21-3p 可靶向钙/钙调蛋白依赖性蛋白激酶 2（CAMKK2），其过表达可抑制 CAMKK2 的表达及其下游的腺苷 5'-单磷酸（AMP）激活蛋白激酶（AMPK）的磷酸化，从而抑制 OL-FS13 对 OGD/R 和 CI/R 的治疗作用。CAMKK2 的抑制也拮抗了 OL-FS13 对核因子红细胞 2 相关因子 2（Nrf-2）的上调，从而消除了该肽的抗氧化活性。
我们的结果表明，OL-FS13 通过抑制 miR-21-3p 激活 CAMKK2/AMPK/Nrf-2 轴来减轻 OGD/R 和 CI/R。
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