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Neuroprotective effects of atypical D-1 receptor agonist SKf83959 are mediated via D-1 receptor-dependent inhibition of glycogen synthase kinase-3 beta and a receptor-independent anti-oxidative action

文献类型：期刊论文

作者Yu, Yang2; Wang, Jing-Ru2; Sun, Pei-Hua2; Guo, Yang2; Zhang, Zhang-Jin1; Jin, Guo-Zhang2; Zhen, Xuechu2
刊名JOURNAL OF NEUROCHEMISTRY
出版日期2008-02
卷号104期号:4页码:946-956
关键词apoptosis dopamine receptor glycogen synthase kinase-3 beta neuroprotection nitric oxide 3-methyl-6-chloro-7,8-hydroxy-1-(3-methylphenyl)-2,3,4,5-tetrahydro-1H3-benzazepine
ISSN号0022-3042
DOI10.1111/j.1471-4159.2007.05062.x
文献子类Article
英文摘要3-methyl-6-chloro-7,8-hydroxy-1-(3-methylphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine (SKF83959), a selective agonist for the putative phosphatidylinositol (PI)-linked dopamine receptor (DAR), has been shown to possess potent anti-Parkinson disease effects but produces less dyskinesia and motor fluctuation that are frequently observed in Parkinson disease drug therapies. The present study was designed to detect the neuroprotection of SKF83959 and its potential mechanism for the effect in cultured rat cortical cells. The presence of SKF83959 with a dose range of 0.1-30 mu mol/L improved H2O2-reduced cell viability in a dose-dependent manner. The anti-apoptotic action of SKF83959 was partially abolished by pre-application of the D-1 antagonist SCH23390 (30 mu mol/L) and the PI 3-kinase (PI 3-K) inhibitor LY294002 but not by the MEK1/2 inhibitor PD98059 (30 mu mol/L). Moreover, SKF83959 treatment significantly inhibited H2O2-activated glycogen synthase kinase-3 beta (GSK-3 beta) which was associated with the drug's neuroprotective effect, but this inhibition was attenuated by SCH23390 and a selective PI 3-K inhibitor. Moreover, the application of either SKF83959 or a pharmacological inhibitor of GSK-3 beta attenuated the inhibition by H2O2 on the expression of inducible NO synthase and production of NO. This indicates that D-1-like receptor, presumably PI-linked D-1 receptor, -mediated alteration of PI 3-K/ Akt/GSK-3 beta pathway is involved in the neuroprotection by SKF83959. In addition, SKF83959 also effectively decreased the level of the lipid peroxidation and increased the activity of GSH-peroxidase altered by H2O2.. These results suggest that SKF83959 exerts its neuroprotective effect through both receptor-dependent and independent mechanisms: Inhibition of GSK-3 beta and consequently increasing the expression of inducible NO synthase via putative PI-linked DAR; and its anti-oxidative activity which is independent of DAR.
WOS关键词GLYCOGEN-SYNTHASE KINASE-3-BETA ; PARKINSONS-DISEASE ; NITRIC-OXIDE ; DOPAMINE-RECEPTOR ; MOTOR FLUCTUATIONS ; VARYING EFFICACIES ; ADENYLYL-CYCLASE ; OXIDATIVE STRESS ; RAT-BRAIN ; ACTIVATION
WOS研究方向Biochemistry & Molecular Biology ; Neurosciences & Neurology
语种英语
WOS记录号WOS:000253673400008
出版者BLACKWELL PUBLISHING
源URL[http://119.78.100.183/handle/2S10ELR8/272997]  
专题药理学第二研究室
中科院受体结构与功能重点实验室
新药研究国家重点实验室
通讯作者Zhen, Xuechu
作者单位1.Univ Hong Kong, Sch Chinese Med, Hong Kong, Hong Kong, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China;
推荐引用方式
GB/T 7714		 Yu, Yang,Wang, Jing-Ru,Sun, Pei-Hua,et al. Neuroprotective effects of atypical D-1 receptor agonist SKf83959 are mediated via D-1 receptor-dependent inhibition of glycogen synthase kinase-3 beta and a receptor-independent anti-oxidative action[J]. JOURNAL OF NEUROCHEMISTRY,2008,104(4):946-956.
APA Yu, Yang.,Wang, Jing-Ru.,Sun, Pei-Hua.,Guo, Yang.,Zhang, Zhang-Jin.,...&Zhen, Xuechu.(2008).Neuroprotective effects of atypical D-1 receptor agonist SKf83959 are mediated via D-1 receptor-dependent inhibition of glycogen synthase kinase-3 beta and a receptor-independent anti-oxidative action.JOURNAL OF NEUROCHEMISTRY,104(4),946-956.
MLA Yu, Yang,et al."Neuroprotective effects of atypical D-1 receptor agonist SKf83959 are mediated via D-1 receptor-dependent inhibition of glycogen synthase kinase-3 beta and a receptor-independent anti-oxidative action".JOURNAL OF NEUROCHEMISTRY 104.4(2008):946-956.

入库方式： OAI收割

来源：上海药物研究所

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