原创力文档unexpected neuronal protection of su5416 against 1-methyl-4-phenylpyridinium ion-induced toxicity via inhibiting neuronal nitric oxide synthase意想不到的神经保护su5416反对1-methyl-4-phenylpyridinium离子感应通过抑制神经元一氧化氮合酶的毒性.pdfVIP
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unexpected neuronal protection of su5416 against 1-methyl-4-phenylpyridinium ion-induced toxicity via inhibiting neuronal nitric oxide synthase意想不到的神经保护su5416反对1-methyl-4-phenylpyridinium离子感应通过抑制神经元一氧化氮合酶的毒性
Unexpected Neuronal Protection of SU5416 against 1-
Methyl-4-Phenylpyridinium Ion-Induced Toxicity via
Inhibiting Neuronal Nitric Oxide Synthase
1. 2,3. 1¤ 1 1 1
Wei Cui , Zaijun Zhang , Wenming Li , Shinghung Mak , Shengquan Hu , Huan Zhang ,
2 4 1 2 1
Shuai Yuan , Jianhui Rong , Tony Chunglit Choi , Simon M. Y. Lee *, Yifan Han *
1 Department of Applied Biology and Chemical Technology, Institute of Modern Medicine, The Hong Kong Polytechnic University, Hong Kong, China, 2 State Key
Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China, 3 Institute of New Drug Research,
Guangdong Province Key Laboratory of Pharmacodynamic, Constituents of Traditional Chinese Medicine New Drug Research, College of Pharmacy, Jinan University,
Guang Zhou, Guangdong, China, 4 School of Chinese Medicine, the University of Hong Kong, Hong Kong, China
Abstract
SU5416 was originally designed as a potent and selective inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-
2) for cancer therapy. In this study, we have found for the first time that SU5416 unexpectedly prevented 1-methyl-4-
phenylpyridinium ion (MPP+)-induced neuronal apoptosis in cerebellar granule neurons, and decreased 1-methyl-4-phenyl-
1,2,3,6-tetrahydropyridine (MPTP)-induced loss of dopaminergic neurons and impairment of swimming behavior in
zebrafish in a concentration-dependent manner. However, VEGFR-2 kinase inhibitor II, another specific VEGFR-2 inhibitor,
failed to reverse neurotoxicity
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