Abstract
Trehalose Inhibits Oxygen Glucose Deprivation Induced Autophagic Death in Dopaminergic SH-SY5Y Cells via Mitigation of Glycolysis Dysfunction and Inhibiting Activated Protein Kinase Activation
Department of Neurology, Hongqi Hospital Affiliated to Mudanjiang Medical University, 1Heilongjiang Key Laboratory of Ischemic Stroke Prevention and Treatment, Mudanjiang, Heilongjiang Province 157011, 2Department of Physiology, Heilongjiang Traditional Chinese Medicine University Jiamusi college, Jiamusi, Heilongjiang Province 154007, 3Department of Neurology, Jinnan Hospital, Tianjin 300350, China
Correspondence Address:
Changhao Yin, Heilongjiang Key Laboratory of Ischemic Stroke Prevention and Treatment, Mudanjiang, Heilongjiang Province 157011, China, E-mail: yinchanghao79623@163.com
The goal of this study was to explore the regulatory mechanism of trehalose on the autophagy death of SHSY5Y cells induced by oxygen and sugar deprivation from the aspect of glycolysis. Human SH-SY5Y cells were divided into three groups includes control group (control), model group (oxygen and sugar deprivation) and experimental group (oxygen and sugar deprivation+trehalose). The proliferation activity, mortality of SH-SY5Y cells, adenosine triphosphate and pyruvic acid were measured. Western blot was carried out to detect the expression levels of autophagic-related proteins (Unc-51 like autophagy activating kinase 1, beclin 1, autophagy related 5, microtubule-associated protein 1A/1B-light chain 3, ubiquitin-binding protein p62), glycolysis-related proteins (hexokinase 2, phosphofructokinase, pyruvate kinase M2) and activated protein kinase signalling pathway proteins. Compared with the control group, the autophagy level of the oxygen and sugar deprivation group was increased in a time-dependent manner (p<0.05). Cell mortality was increased (p<0.05) and the expressions of hexokinase 2, phosphofructokinase, pyruvate kinase M2 were decreased (p<0.05). The expression levels of activated protein kinase signalling pathway related proteins was upregulated (p<0.05). On the contrary, the cell death rate and autophagy level of the experimental group were significantly lower than that of the model group. The protein levels of hexokinase 2, phosphofructokinase, pyruvate kinase M2 were up-regulated and the difference was statistically significant (p<0.05). Trehalose can reduce the damage of SH-SY5Y cells caused by oxygen and sugar deprivation. The mechanism may be related to the improvement of glycolysis dysfunction and alleviation of autophagy over activation of activated protein kinase.