Mechanism of mitochondrial protection by the Buyin Qianzheng formula in a Parkin overexpression cell model  

作　　者：Cuicui Cheng Yushan Gao Cong Gai Wandi Feng Haojie Ma Jing Feng Zhenyu Guo Shujing Zhang Jie Wu Hongmei Sun 

机构地区：[1]School of Traditional Chinese Medicine,Beijing University of Chinese Medicine,Beijing,102488,China [2]Institute of Health Sciences,National Engineering Research Center for Beijing Biochip Technology,Beijing,102206,China [3]Department of Physiology,Mayo Clinic Hospital,Phoenix,85054,USA

出　　处：《Journal of Traditional Chinese Medical Sciences》2022年第1期59-68,共10页中医科学杂志（英文）

基　　金：This work is supported by the National Natural Science Foundation of China(81774110 and 81573773).

摘　　要：Objective:To identify the molecular mechanisms of the effects of the Buyin Qianzheng formula(BYQZF)on the mitochondrial dynamics in a Parkin overexpression Parkinson's disease(PD)cell model.Methods:First,a stable Parkin overexpression cell model was constructed using plasmid transfection.Then,we examined the protective effect of BYQZF on the mitochondrial dysfunction of the Parkin overexpression PD cell model induced by neurotoxin 1-methyl-4-phenylpyridinium ion(MPPþ).The mRNA expression level of Parkin was evaluated using real-time quantitative PCR.The cell survival rate was detected using the Cell Counting Kit-8 assay.We evaluated the cellular adenosine triphosphate(ATP)levels using luciferase assays.A laser scanning confocal microscope was used to observe the mitochondrial morphology,activity,and mitochondrial membrane potential(DJm).Western blot was conducted to evaluate the levels of the fusion proteins mitofusin1,mitofusin2,optic atrophy 1,dynaminrelated protein 1,and mitochondrial fission protein 1.Results:Parkin overexpression attenuated MPPþ-induced mitochondrial damage,increased mitochondrial activity and DJm.BYQZF increased the survival of MPPþ-induced cells that overexpressed Parkin and upregulated the mitochondrial form factor and activity.It also inhibited a decrease in the DJm and ATP levels.These findings suggested that BYQZF protected against MPPþ-induced mitochondrial dysfunction and enhanced the protective effect of Parkin overexpression.Furthermore,the formula upregulated the expression of the fusion proteins mitofusin1,mitofusin2,and optic atrophy 1(closely related to mitochondrial quality remodeling),and reduced the expression of the fission protein dynamicrelated protein 1,as well as mitochondrial fission protein 1.Conclusion:The mechanism by which BYQZF increased the mitochondrial protective effect of Parkin gene overexpression in MPPþ-induced cells may be related to improving mitochondrial function and regulating the balance of mitochondrial division and fusion proteins.

关 键 词：Parkinson's disease Parkin overexpression Mitochondria Buyin Qianzheng formula Neurotoxin 1-methyl-4-phenylpyridinium ion SH-SY5Y Mitofusin 2 Dynamic-related protein 1 

分 类 号：R74[医药卫生—神经病学与精神病学]