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SIRT3 Inhibits Mitophagy and Alleviates Neuronal Oxygen Deprivation/Reoxygenation Injury Aggravated by High Glucose |
Chen-yang ZHANG1,Chang-chun HEI2,Shi-lin YUAN1,Yu-jia ZHOU1,Mei-ling CAO1,Yi-xin QIN1,Xiao YANG3,**() |
1 School of Clinical Medicine, Ningxia Medical University, Yinchuan 750004, China 2 Department of Human Anatomy, Histology and Embryology, Ningxia Medical University, Yinchuan 750004, China 3 Neuroscience Center, General Hospital of Ningxia Medical University, Yinchuan 750004, China |
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Abstract Objective: To investigate whether high glucose can aggravate oxygen deprivation/reoxygenation (OD/R) injury in neurons through regulating mitophagy and the specific molecular mechanism of regulating mitophagy. Methods: HT22 cells are used to establish a model of cellular oxygen deprivation/reoxygenation to simulate cerebral ischemia/reperfusion injury in vivo. And cells are treated with high glucose medium (HG 50 mmol/L). 3-TYP is given to inhibit the expression of SIRT3. CCK8 is used to examine cell viability; flow cytometry is used to detect cell apoptosis, and TMRE fluorescence detection kit is used to detect cell MMP; Western blot is used to detect the expression of mitochondrial division/fusion related protein (DRP1, OPA1, TOM20), autophagy related protein (LC3Ⅱ, Beclin-1), mitophagy related protein (PINK1, Parkin) and SIRT3. Results: Compared with OD groups, the cell density is further reduced, the cell contour is more blurred, the synapses are shortened, the floating cells increase in HG+OD groups, and cells in HG+OD groups have lower survival rate and higher apoptosis rate (P<0.05). Compared with OD groups, cells in HG+OD groups have lower MMP (P<0.05). Compared with OD groups, the expression of P-DRP1 in HG+OD groups is increased, but OPA1 and TOM20 are decreased (P<0.05); the expression of Beclin-1 and LC3Ⅱ as well as PINK1 and Parkin in HG+OD groups are also increased (P<0.05). Furthermore, SIRT3 protein and gene are further increased in HG+OD groups (P<0.05). 3-TYP treatment can further aggravate the OD/R injury of neurons in HG groups. And 3-TYP also increases the expression of DRP1, LC3Ⅱ and PINK1. Conclusions: High glucose can aggravate oxygen deprivation/reoxygenation injury in neurons by exacerbation of cell apoptosis, reduction of MMP and activation of mitophagy. In addition, SIRT3 can inhibit PINK1-Parkin pathway-mediated mitophagy and alleviate high glucose aggravated-neuronal OD/R injury.
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Received: 15 June 2021
Published: 01 December 2021
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Corresponding Authors:
Xiao YANG
E-mail: cckk606@sina.com
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