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学科主题基础医学
Neuroglobin Promotes Neurite Outgrowth via Differential Binding to PTEN and Akt
Li, Li1,2,3; Liu, Qian Rong1,2,3; Xiong, Xin Xin1,2,3; Liu, Ju Mei1,2,3; Lai, Xiao Jing1,2,3; Cheng, Chun1,2,3; Pan, Feng1,2,3; Chen, Yong1,2,3; Yu, Shang Bin1,2,3; Yu, Albert Cheung Hoi4,5,6; Chen, Xiao Qian1,2,3
关键词Ngb Neuron Axon Regeneration PI3K/Akt
刊名MOLECULAR NEUROBIOLOGY
2014-02-01
DOI10.1007/s12035-013-8506-7
49期:1页:149-162
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Neurosciences
资助者National Natural Science Fund of China ; National Natural Science Fund of China
研究领域[WOS]Neurosciences & Neurology
关键词[WOS]NUCLEOTIDE DISSOCIATION INHIBITOR ; SIGNALING PATHWAYS ; ASTROCYTES ; GROWTH ; PHOSPHORYLATION ; NEURITOGENESIS ; 14-3-3-GAMMA ; EXPRESSION ; REDUCTION ; ISCHEMIA
英文摘要

Neuroglobin, the third mammalian globin with a hexa-coordinated heme, exists predominantly in neurons of the brain. Neuroglobin plays an important role in neuronal death upon ischemia and oxidative stress. The physiological function of neuroglobin remains unclear. Here, we report a novel function of neuroglobin in neurite development. Knocking-down neuroglobin exhibited a prominent neurite-deficient phenotype in mouse neuroblastoma N2a cells. Silencing neuroglobin prevented neurite outgrowth, while ectopic expression of neuroglobin but not homologous cytoglobin promoted neurite outgrowth of N2a cells upon serum withdrawal. In primary cultured rat cerebral cortical neurons, neuroglobin was upregulated and preferentially distributed in neurites during neuronal development. Overexpression of neuroglobin but not cytoglobin in cultured cortical neurons promoted axonal outgrowth, while knocking-down of neuroglobin retarded axonal outgrowth. Neuroglobin overexpression suppressed phosphatase and tensin homolog (PTEN) but increased Akt phosphorylation during neurite induction. Bimolecular fluorescence complementation and glutathione S-transferase pull-down assays revealed that neuroglobin and various mutants (E53Q, E118Q, K119N, H64A, H64L, and Y44D) bound with Akt and PTEN differentially. Neuroglobin E53Q showed a prominent reduced PTEN binding but increased Akt binding, resulting in decreased p-PTEN, increased p-Akt, and increased neurite length. Taken together, we demonstrate a critical role of neuroglobin in neuritogenesis or development via interacting with PTEN and Akt differentially to activate phosphatidylinositol 3-kinase/Akt pathway, providing potential therapeutic applications of neuroglobin for axonopathy in neurological diseases.

语种英语
所属项目编号30570555 ; 81070937 ; 81172397
资助者National Natural Science Fund of China ; National Natural Science Fund of China
WOS记录号WOS:000331046800013
Citation statistics
Cited Times:16[WOS]   [WOS Record]     [Related Records in WOS]
文献类型期刊论文
版本出版稿
条目标识符http://ir.bjmu.edu.cn/handle/400002259/53995
Collection北京大学基础医学院_神经生物学系
作者单位1.Huazhong Univ Sci & Technol, Tongji Med Coll, Sch Basic Med, Dept Pathophysiol, Wuhan 430032, Peoples R China
2.Huazhong Univ Sci & Technol, Minist Educ, Key Lab Neurol Dis, Wuhan 430032, Peoples R China
3.Huazhong Univ Sci & Technol, Hubei Prov Key Lab Neurol Dis, Wuhan 430032, Peoples R China
4.Peking Univ, Sch Basic Med Sci, Neurosci Res Inst, Beijing 100871, Peoples R China
5.Peking Univ, Sch Basic Med Sci, Dept Neurobiol, Beijing 100871, Peoples R China
6.Peking Univ, Minist Educ, Natl Hlth & Family Planning Commiss, Key Lab Neurosci, Beijing 100871, Peoples R China
Recommended Citation
GB/T 7714
Li, Li,Liu, Qian Rong,Xiong, Xin Xin,et al. Neuroglobin Promotes Neurite Outgrowth via Differential Binding to PTEN and Akt[J]. MOLECULAR NEUROBIOLOGY,2014,49(1):149-162.
APA Li, Li.,Liu, Qian Rong.,Xiong, Xin Xin.,Liu, Ju Mei.,Lai, Xiao Jing.,...&Chen, Xiao Qian.(2014).Neuroglobin Promotes Neurite Outgrowth via Differential Binding to PTEN and Akt.MOLECULAR NEUROBIOLOGY,49(1),149-162.
MLA Li, Li,et al."Neuroglobin Promotes Neurite Outgrowth via Differential Binding to PTEN and Akt".MOLECULAR NEUROBIOLOGY 49.1(2014):149-162.
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