期刊
CELLULAR AND MOLECULAR NEUROBIOLOGY
卷 37, 期 4, 页码 655-664出版社
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s10571-016-0402-z
关键词
Indirubin-3-oxime; H2O2; GSK3 beta; PI3-K; ERK
资金
- Natural Science Foundation of Zhejiang Province [LY15H310007]
- Research Grants Council of Hong Kong [561011, 15101014]
- Applied Research Project on Nonprofit Technology of Zhejiang Province [2016C37110]
- National Natural Science Foundation of China [U1503223, 81202150, 81471398]
- Ningbo International Science and Technology Cooperation Project [2014D10019]
- Ningbo municipal innovation team of life science and health [2015C110026]
- Ningbo Natural Science Foundation [2015A610219]
- Scientific Research Foundation for the Returned Overseas Chinese Scholars, the State Education Ministry
- K. C. Wong Magna Fund in Ningbo University
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 3 beta (GSK3 beta) 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/GSK3 beta cascade and the ERK pathway induced by H2O2. In addition, both GSK3 beta 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 GSK3 beta 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.
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