Neural Regeneration Research ›› 2021, Vol. 16 ›› Issue (6): 1044-1051.doi: 10.4103/1673-5374.300725

Previous Articles     Next Articles

Apelin-13 inhibits apoptosis and excessive autophagy in cerebral ischemia/reperfusion injury

Zi-Qi Shao1, Shan-Shan Dou2, Jun-Ge Zhu1, Hui-Qing Wang1, Chun-Mei Wang2, Bao-Hua Cheng2, *, Bo Bai2, *#br#   

  1. 1 Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, China;  2 Neurobiology Institute, Jining Medical University, Jining, Shandong Province, China
  • Online:2021-06-15 Published:2020-12-31
  • Contact: Bao-Hua Cheng, PhD, chengbh1979@163.com; Bo Bai, PhD, bbai@mail.jnmc.edu.cn.
  • Supported by:
    The study was supported by the National Natural Science Foundation of China, Nos. 81870948 (to BB), 81671276 (to BHC), 81501018 (to CMW); the Natural Science Foundation of Shandong Province of China, No. ZR2014HL040 (to BHC); Program Supporting Foundation for Teachers’ Research of Jining Medical University of China, No. JYFC2018KJ003 (to SSD).

PDF

480

Abstract: Apelin-13 is a novel endogenous ligand for an angiotensin-like orphan G-protein coupled receptor, and it may be neuroprotective against cerebral ischemia injury. However, the precise mechanisms of the effects of apelin-13 remain to be elucidated. To investigate the effects of apelin-13 on apoptosis and autophagy in models of cerebral ischemia/reperfusion injury, a rat model was established by middle cerebral artery occlusion. Apelin-13 (50 µg/kg) was injected into the right ventricle as a treatment. In addition, an SH-SY5Y cell model was established by oxygen-glucose deprivation/reperfusion, with cells first cultured in sugar-free medium with 95% N2 and 5% CO2 for 4 hours and then cultured in a normal environment with sugar-containing medium for 5 hours. This SH-SY5Y cell model was treated with 10–7 M apelin-13 for 5 hours. Results showed that apelin-13 protected against cerebral ischemia/reperfusion injury. Apelin-13 treatment alleviated neuronal apoptosis by increasing the ratio of Bcl-2/Bax and significantly decreasing cleaved caspase-3 expression. In addition, apelin-13 significantly inhibited excessive autophagy by regulating the expression of LC3B, p62, and Beclin1. Furthermore, the expression of Bcl-2 and the phosphatidylinositol-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway was markedly increased. Both LY294002 
(20 µM) and rapamycin (500 nM), which are inhibitors of the PI3K/Akt/mTOR pathway, significantly attenuated the inhibition of autophagy and apoptosis caused by apelin-13. In conclusion, the findings of the present study suggest that Bcl-2 upregulation and mTOR signaling pathway activation lead to the inhibition of apoptosis and excessive autophagy. These effects are involved in apelin-13-induced neuroprotection against cerebral ischemia/reperfusion injury, both in vivo and in vitro. The study was approved by the Animal Ethical and Welfare Committee of Jining Medical University, China (approval No. 2018-JS-001) in February 2018.  

Key words: central nervous system, brain, brain injury, factor, pathways, apoptosis, autophagy, neuroprotection, regeneration