Heparanase enhances nerve-growth-factor-induced PC12 cell neuritogenesis via the p38 MAPK pathway

doi:10.1042/BJ20110167

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第三研究室

	Heparanase enhances nerve-growth-factor-induced PC12 cell neuritogenesis via the p38 MAPK pathway
	Cui, Hengxiang 2; Shao, Chenghao 3; Liu, Qin 2; Yu, Wenjie 1,4; Fang, Jianping 2; Yu, Weishi 1,4; Ali, Amjad 1,4; Ding, Kan2
刊名	BIOCHEMICAL JOURNAL
	2011-12-01
卷号	440 页码:273-282
关键词	heparanase neurite outgrowth neuritogenesis neuron differentiation p38 mitogen-activated protein kinase (MAPK)
ISSN号	0264-6021
DOI	10.1042/BJ20110167
文献子类	Article
英文摘要	Heparanase is involved in the cleavage of the HS (heparan sulfate) chain of HSPGs (HS proteoglycans) and hence participates in remodelling of the ECM (extracellular matrix) and BM (basement membrane). In the present study we have shown that NGF (nerve growth factor) promoted nuclear enrichment of EGR1 (early growth response 1), a transcription factor for heparanase, and markedly induced heparanase expression in rat adrenal pheochromocytoma (PC12) cells. K252a, an antagonist of the NGF receptor TrkA (tyrosine kinase receptor A), decreased heparanase protein expression induced by NGF in PC12 cells. Suramin, a heparanase inhibitor, decreased heparanase in PC12 cells and blocked NGF-induced PC12 neuritogenesis. Stable overexpression of heparanase activated p38 MAPK (mitogen-activated protein kinase) by phosphorylation and enhanced the neurite outgrowth induced by NGF, whereas knock down of heparanase impaired this process. However, overexpression of latent pro-heparanase with a Y156A mutation still led to enhanced NGF-induced neurite outgrowth and increased p38 MAPK phosphorylation. Inhibition of p38 MAPK by SB203580 suppressed the promotion of NGF-induced neuritogenesis by the wild-type and mutant heparanase. The impaired differentiation by knock down of heparanase could be restored by transfection of wild-type or mutant heparanase in PC12 cells. The results of the present study suggest that heparanase, at least in the nonenzymatic form, may promote NGF-induced neuritogenesis via the p38 MAPK pathway.
资助项目	National Natural Science Foundation of China[30770484] ; National Science and Technology Major Project "Key New Drug Creation and Manufacturing Program"[2009ZX09301-001] ; National Science and Technology Major Project "Key New Drug Creation and Manufacturing Program"[2009ZX09501-011] ; National Science and Technology Major Project "Key New Drug Creation and Manufacturing Program"[2009ZX09103-071]
WOS关键词	SULFATE PROTEOGLYCANS ; EXTRACELLULAR-MATRIX ; CANCER-CELLS ; NEURONAL DIFFERENTIATION ; GENE-TRANSCRIPTION ; NEURITE OUTGROWTH ; FACTOR EXPRESSION ; ADULT RATS ; DEGRADATION ; ACTIVATION
WOS研究方向	Biochemistry & Molecular Biology
语种	英语
出版者	PORTLAND PRESS LTD
WOS记录号	WOS:000298222200011
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/278310]
专题	药理学第三研究室
通讯作者	Ding, Kan
作者单位	1.E China Normal Univ, Inst Biomed Sci, Shanghai 200241, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Glycochem & Glycobiol Lab, Shanghai 201203, Peoples R China; 3.Changhai Hosp, Dept Surg, Shanghai 200433, Peoples R China; 4.E China Normal Univ, Sch Life Sci, Shanghai 200241, Peoples R China
推荐引用方式 GB/T 7714	Cui, Hengxiang,Shao, Chenghao,Liu, Qin,et al. Heparanase enhances nerve-growth-factor-induced PC12 cell neuritogenesis via the p38 MAPK pathway[J]. BIOCHEMICAL JOURNAL,2011,440:273-282.
APA	Cui, Hengxiang.,Shao, Chenghao.,Liu, Qin.,Yu, Wenjie.,Fang, Jianping.,...&Ding, Kan.(2011).Heparanase enhances nerve-growth-factor-induced PC12 cell neuritogenesis via the p38 MAPK pathway.BIOCHEMICAL JOURNAL,440,273-282.
MLA	Cui, Hengxiang,et al."Heparanase enhances nerve-growth-factor-induced PC12 cell neuritogenesis via the p38 MAPK pathway".BIOCHEMICAL JOURNAL 440(2011):273-282.