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Title: Activation of Phosphatidylinositol-Linked D-1-Like Receptor Modulates FGF-2 Expression in Astrocytes via IP3-Dependent Ca2+ Signaling
Author: Zhang, Xinhua ; Zhou, Zheng ; Wang, Dakui ; Li, Aiqun ; Yin, Yanqing ; Gu, Xiaosong ; Ding, Fei ; Zhen, Xuechu ; null(周嘉伟)
Source: JOURNAL OF NEUROSCIENCE
Issued Date: 2009
Volume: 29, Issue:24, Pages:7766-7775
Keyword: D-1 DOPAMINE AGONISTS ; FIBROBLAST-GROWTH-FACTOR ; PARKINSONS-DISEASE ; VARYING EFFICACIES ; RAT-BRAIN ; SUBSTANTIA-NIGRA ; SKF 83959 ; NEURONS ; SKF83959 ; CALCIUM
Subject: Neurosciences & Neurology
Corresponding Author: Zhou, JW (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Neurosci, State Key Lab Neurosci, 320 Yueyang Rd, Shanghai 200031, Peoples R China,xczhen@mail.shcnc.ac.cn ; jwzhou@ion.ac.cn
English Abstract: Fibroblast growth factor-2 (FGF-2) is predominantly synthesized and secreted by astrocytes in adult brain. Our previous study showed that activation of classical dopamine receptor D-1 or D-2 elicits FGF-2 biosynthesis and secretion in astrocytes. Here, we report that astrocytic FGF-2 expression is also regulated by phosphatidylinositol (PI)-linked D-1-like receptor. SKF83959, a selective PI-linked D-1-like receptor agonist, upregulates the levels of FGF-2 protein in striatal astrocyte cultures in classical dopamine D-1 and D-2 receptor-independent manner. The conditional medium derived from SKF83959-activated astrocytes promoted the number of TH+ neurons in vitro. Treatment of astrocytes with SKF83959 increased intracellular calcium in two phases. Inhibition of intracellular calcium oscillation by inositol 1,4,5-triphosphate (IP3) inhibitors blocked the SKF83959-induced increase in FGF-2 expression. Moreover, intraperitoneal administration of SKF83959 reversed l-methyl-4-phenyl-l,2,3,6-tetrahydropypridine (MPTP)-induced reduction in FGF-2 expression in both the striatum and ventral midbrain and resulted in marked protection of dopaminergic neurons from MPTP-induced neurotoxicity. These results indicate that IP3/Ca2+/calmodulin-dependent protein kinase is an uncharted intracellular signaling pathway that is crucial for the regulation of FGF-2 synthesis in astrocytes. PI-linked D-1-like receptor plays an important role in the regulation of astrocytic FGF-2 expression and neuroprotection which may provide a potential target for the drug discovery in Parkinson's disease.
Indexed Type: sci
Language: 英语
Content Type: 期刊论文
URI: http://ir.sibs.ac.cn/handle/331001/1657
Appears in Collections:神经所(总)_期刊论文
基底神经节的发育与退行性疾病研究组_期刊论文

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Zhang, Xinhua; Zhou, Zheng; Wang, Dakui; Li, Aiqun; Yin, Yanqing; Gu, Xiaosong; Ding, Fei; Zhen, Xuechu; Zhou, Jiawei.Activation of Phosphatidylinositol-Linked D-1-Like Receptor Modulates FGF-2 Expression in Astrocytes via IP3-Dependent Ca2+ Signaling,JOURNAL OF NEUROSCIENCE,2009,29(24):7766-7775
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