1. Dexmedetomidine Confers Protection Against Neuronal Oxygen Glucose Deprivation-Reperfusion by Regulating SIRT3 Mediated Autophagy.
- Author
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Fu Z, Pang Z, He L, Zhang L, Fan Y, Zhao C, and Yang J
- Subjects
- AMP-Activated Protein Kinases metabolism, Acridine Orange metabolism, Acridine Orange pharmacology, Adenosine Triphosphate metabolism, Apoptosis, Autophagy, Autophagy-Related Proteins metabolism, Glucose metabolism, Humans, Hydrogen Peroxide pharmacology, Neurons metabolism, Oxygen metabolism, Reperfusion, Signal Transduction, TOR Serine-Threonine Kinases metabolism, Dexmedetomidine pharmacology, Reperfusion Injury drug therapy, Reperfusion Injury metabolism, Reperfusion Injury prevention & control, Sirtuin 3 metabolism
- Abstract
Dexmedetomidine (Dex) plays protective effects on brain ischemia-reperfusion (I/R) injury, but its mechanism remains unclear. In this study, we aimed to investigate whether Dex protects neurons against I/R injury by activating SIRT3 mediated autophagy. The oxygen glucose deprivation-reperfusion (OGD/R) model was constructed in HT22 cells. Different doses of Dex (50 ng/mL, 100 ng/mL and 500 ng/mL) were treated to observe the changes of autophagy and SIRT3 expression. Further, the mimic of SIRT3 and SIRT3 inhibitor were used to analyze the effects of Dex on the SIRT3 expression in HT22 cells. Additionally, the autophagy inhibitor and AMPK inhibitor were used to analyze the effects of Dex on SIRT3 mediated autophagy. The cells viability, oxidative stress and ATP were observed using assay kits. The mitochondrial membrane potential (MMP) and death were analyzed by flow cytometry. The degree of autophagy was observed by acridine orange staining. Western blotting was used to analyze the expression of autophagy related proteins and AMPK/mTOR pathway related proteins. After Dex treatment, the OGD/R induced cell injury was significantly improved through decreasing the levels of LDH and H
2 O2 , increasing levels of ATP and MMP. Furthermore, Dex increased the degree of autophagy and expression of SIRT3 in OGD/R injured cells. Through overexpression of SIRT3, the OGD/R induced cell injury was also clearly improved. But the SIRT3 inhibitor or autophagy inhibitor covered the roles of Dex. Additionally, AMPK inhibitor played an opposite role compared with the effects of Dex treatment. From this study, the protection mechanism of Dex on neurons I/R injury might related to the activation of SIRT3 mediated autophagy., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)- Published
- 2022
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