机构:[1]Ningbo Key Laboratory of Behavioral Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo 315211, China[2]Ningbo Xiaoshi High School, Ningbo 315010, China[3]Department of Applied Biology and Chemistry Technology, Institute of Modern Chinese Medicine, The Hong Kong Polytechnic University, Hong Kong SAR, China[4]The Affiliated Yinzhou Hospital, School of Medicine, Ningbo University, Ningbo 315211, China[5]Institute of New Drug Research, Guangdong Province Key Laboratory of Pharmacodynamic, Constituents of Traditional Chinese Medicine and New Drug Research, College of Pharmacy, Jinan University, Guangdong, China[6]State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China[7]Division of Life Science and Center for Chinese Medicine, The Hong Kong University of Science and Technology, Hong Kong, China
Oxidative stress-induced neuronal apoptosis plays an important role in many neurodegenerative disorders. In this study, we have shown that indirubin-3-oxime, a derivative of indirubin originally designed for leukemia therapy, could prevent hydrogen peroxide (H2O2)-induced apoptosis in both SH-SY5Y cells and primary cerebellar granule neurons. H2O2 exposure led to the increased activities of glycogen synthase kinase 3β (GSK3β) and extracellular signal-regulated kinase (ERK) in SH-SY5Y cells. Indirubin-3-oxime treatment significantly reversed the altered activity of both the PI3-K/Akt/GSK3β cascade and the ERK pathway induced by H2O2. In addition, both GSK3β and mitogen-activated protein kinase inhibitors significantly prevented H2O2-induced neuronal apoptosis. Moreover, specific inhibitors of the phosphoinositide 3-kinase (PI3-K) abolished the neuroprotective effects of indirubin-3-oxime against H2O2-induced neuronal apoptosis. These results strongly suggest that indirubin-3-oxime prevents H2O2-induced apoptosis via concurrent inhibiting GSK3β and the ERK pathway in SH-SY5Y cells, providing support for the use of indirubin-3-oxime to treat neurodegenerative disorders caused or exacerbated by oxidative stress.
基金:
This work was supported by the Natural Science
Foundation of Zhejiang Province (LY15H310007), Research Grants
Council of Hong Kong (561011 & 15101014), the Applied Research
Project on Nonprofit Technology of Zhejiang Province
(2016C37110), the National Natural Science Foundation of China
(U1503223, 81202150, 81471398), the Ningbo International Science
and Technology Cooperation Project (2014D10019), Ningbo municipal
innovation team of life science and health (2015C110026),
Ningbo Natural Science Foundation (2015A610219), the Scientific
Research Foundation for the Returned Overseas Chinese Scholars, the
State Education Ministry, and the K. C. Wong Magna Fund in Ningbo
University.
语种:
外文
PubmedID:
中科院(CAS)分区:
出版当年[2016]版:
大类|3 区生物
小类|4 区细胞生物学4 区神经科学
最新[2025]版:
大类|4 区医学
小类|4 区细胞生物学4 区神经科学
第一作者:
第一作者机构:[1]Ningbo Key Laboratory of Behavioral Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo 315211, China
通讯作者:
推荐引用方式(GB/T 7714):
Jie Yu,Jiacheng Zheng,Jiajia Lin,et al.Indirubin-3-Oxime Prevents H2O2-Induced Neuronal Apoptosis via Concurrently Inhibiting GSK3β and the ERK Pathway.[J].Cellular and molecular neurobiology.2017,37(4):655-664.doi:10.1007/s10571-016-0402-z.
APA:
Jie Yu,Jiacheng Zheng,Jiajia Lin,Linlu Jin,Rui Yu...&Qinwen Wang.(2017).Indirubin-3-Oxime Prevents H2O2-Induced Neuronal Apoptosis via Concurrently Inhibiting GSK3β and the ERK Pathway..Cellular and molecular neurobiology,37,(4)
MLA:
Jie Yu,et al."Indirubin-3-Oxime Prevents H2O2-Induced Neuronal Apoptosis via Concurrently Inhibiting GSK3β and the ERK Pathway.".Cellular and molecular neurobiology 37..4(2017):655-664