1. Academic Validation
  2. Apelin-36 Protects HT22 Cells Against Oxygen-Glucose Deprivation/Reperfusion-Induced Oxidative Stress and Mitochondrial Dysfunction by Promoting SIRT1-Mediated PINK1/Parkin-Dependent Mitophagy

Apelin-36 Protects HT22 Cells Against Oxygen-Glucose Deprivation/Reperfusion-Induced Oxidative Stress and Mitochondrial Dysfunction by Promoting SIRT1-Mediated PINK1/Parkin-Dependent Mitophagy

  • Neurotox Res. 2021 Jun;39(3):740-753. doi: 10.1007/s12640-021-00338-w.
Ziqi Shao 1 Shanshan Dou 2 Junge Zhu 3 Huiqing Wang 1 Dandan Xu 1 Chunmei Wang 2 Baohua Cheng 4 Bo Bai 2
Affiliations

Affiliations

  • 1 Cheeloo College of Medicine, Shandong University, Jinan, 250014, China.
  • 2 Neurobiology Institute, Jining Medical University, Jining, 272067, China.
  • 3 Capital Medical University, Beijing, 100000, China.
  • 4 Neurobiology Institute, Jining Medical University, Jining, 272067, China. chengbh1979@163.com.
Abstract

Oxidative stress and mitochondrial dysfunction are involved in cerebral ischemia/reperfusion injury-induced neuronal Apoptosis. Mitophagy is the main method to eliminate dysfunctional mitochondria. Apelin-36, a type of neuropeptide, has been reported to exert protective effects in cerebral I/R (I/R) injury, but its precise mechanisms remain to be elucidated. To study the effects of Apelin-36 on oxidative stress and mitochondrial dysfunction in cerebral I/R injury, the oxygen-glucose deprivation/reperfusion (OGD/R) model with 6 h of ischemia and 6 h of reperfusion was established in HT22 cells. Results demonstrated that Apelin-36 protected against OGD/R injury by improving cell viability, decreasing the apoptotic cells ratio and increasing the ratio of Bcl-2/Bax. In addition, Apelin-36 treatment inhibited oxidative stress by downregulating the level of Reactive Oxygen Species (ROS) and malondialdehyde (MDA) as well as the expression of inducible nitric oxide synthase (iNOS). And Apelin-36 also activated the level of superoxide dismutase (SOD) and glutathione (GSH). Mitochondrial Apoptosis was also alleviated with Apelin-36 treatment detected by the mitochondrial membrane potential (MMP) and the expression of Cytochrome c (Cyt c), Cleaved caspase-9, and Cleaved Caspase-3. Furthermore, the SIRT1-mediated PINK1/Parkin-dependent Mitophagy was activated by Apelin-36 treatment with the downregulation of p62 and upregulation of LC3B-II and Beclin1. Both EX527 and Cyclosporine A (CsA), which are inhibitors of SIRT1 and Mitophagy, markedly alleviated the inhibition of oxidative stress and mitochondrial dysfunction caused by Apelin-36. These findings suggest that SIRT1-mediated PINK1/Parkin-dependent Mitophagy is involved in the neuroprotective effects of Apelin-36 on OGD/R-induced oxidative stress and mitochondrial dysfunction.

Keywords

Apelin-36; Mitochondrial dysfunction; Mitophagy; Oxidative stress; Oxygen-glucose deprivation/reperfusion injury.

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