标题:Neuregulin-1beta prevents Ca(2+) overloading and apoptosis through PI3K/Akt activation in cultured dorsal root ganglion neurons with excitotoxicity induced by glutamate.
作者:Liu Z;Li H;Zhang W;Li Y;Liu H;Li Z
作者机构:Department of Anatomy, Shandong University School of Medicine, Jinan 250012, Shandong, China.
通讯作者:Li, ZZ
通讯作者地址:[Li, ZZ]Shandong Univ, Dept Anat, Sch Med, 44 Wenhua Xi Rd, Jinan 250012, Shandong, Peoples R China.
来源:Cellular and Molecular Neurobiology
出版年:2011
卷:31
期:8
页码:1195-1201
DOI:10.1007/s10571-011-9721-2
关键词:Neuregulin-1 beta; Glutamate; Apoptosis; Neurotoxicity; PI3K; Akt;; Dorsal root ganglion
摘要:Neuregulin (NRG) plays an important role on the genesis and differentiation of neurons in the dorsal root ganglion (DRG). Whether NRG-1beta regulates Ca(2+) homeostasis and apoptosis of cultured DRG neurons with excitotoxicity induced by Glu remains unknown. In this study, primary cultured DRG neurons were used to determine the effects of NRG-1beta on Ca(2+) overload and apoptosis of DRG sensory neurons with excitotoxicity induced by Glu. The primary cultured DRG neurons at 48 h of culture age were then exposed to Glu (0.2 mmol/l), Glu (0.2 mmol/l) plus NRG-1beta (20 nmol/l), or Glu (0.2 mmol/l) plus NRG-1beta (20 nmol/l) and phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 (10 mumol/l) for additional 12 h. After that, intracellular Ca(2+) concentration ([Ca(2+)](i)) in isolated DRG neurons using the fluorescent Ca(2+) indicator fluo-3 was measured by confocal laser scanning microscope. Apoptotic neurons were monitored by Hoechst 33342 staining. Expression of caspase-3, procaspase-3, and pAkt was detected by Western blot assay. Administration of 0.2 mmol/l Glu evoked an increase in [Ca(2+)](i), confirming the excitatory effect of Glu. Compared with the control group, apoptotic (condensed and fragmented nuclei) neurons were observed in Glu-treated cells after Hoechst 33342 staining. The increase caspase-3 of and decrease of procaspase-3 expression levels after administration of 0.2 mmol/l Glu suggested the apoptotic effects of Glu. These effects could be inhibited by the presence of NRG-1beta. The effects of NRG-1beta could be blocked by PI3K inhibitor LY294002. These results implicated that NRG-1beta could prevents Ca(2+) overload and apoptosis by activating PI3K/Akt pathway of primary cultured DRG neurons with excitotoxicity induced by Glu.
收录类别:SCIE
WOS核心被引频次:4
资源类型:期刊论文
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