Monocyte-mediated rotenone neurotoxicity towards human neuroblastoma SH-SY5Y: Role of mitogen-activated protein kinases

doi:10.1248/bpb.29.1372

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第二研究室

	Monocyte-mediated rotenone neurotoxicity towards human neuroblastoma SH-SY5Y: Role of mitogen-activated protein kinases
	Zhao, Fei-Li; Hu, Jing-i Hu; Zhu, Xing-Zu
刊名	BIOLOGICAL & PHARMACEUTICAL BULLETIN
	2006-07
卷号	29 期号:7 页码:1372-1377
关键词	rotenone neuroblastoma monocyte apoptosis mitogen-activated protein kinase (MAPK)
ISSN号	0918-6158
DOI	10.1248/bpb.29.1372
文献子类	Article
英文摘要	Increasing evidence has suggested an important role for rotenone in the pathogenesis of Parkinson's disease (PD). In this report, sequential linking of two culture systems, monocytic THP-1 cell line and SH-SY5Y neuroblastoma, was utilized. The supernatant from rotenone-stimulated THP-1 cells was used as the incubating medium for the second culture which adopted cells of the SH-SY5Y neuroblastoma. At 6.25-50 nm, concentrations that were nontoxic to SH-SY5Y directly, rotenone induced dose-dependent cell death on SH-SY5Y through stimulating monocyte THP-1 within a period of 48 h. Cytotoxicity was determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Hoechst 33258 staining revealed that the treatment of SHSY5Y with rotenone-stimulated THP-1 supernatant resulted in condensed nuclei and a decrease in cell size. Apoptotic rate measured by flow cytometric analysis indicated that at 25 and 50 nm, the percentage of apoptotic SH-SY5Y cells accumulated to 31.5% and 37.0% respectively. We further investigated whether rotenone (50 nm) activated mitogen-activated protein kinase (MAPK) cascades, and found it had effect on p38 MAPK and ERK in THP-1 cells, but not JNK. Pretreatment of THP-1 cells with the MAPK kinase inhibitor, PD98059, inhibited THP-1 cell-mediated rotenone neurotoxicity towards SH-SY5Y, whereas the p38 MEK inhibitor, SB203580, had no effect. These results suggested that activation of microglia intracellular signaling pathway may also involve in microglia-enhanced rotenone neurotoxicity.
WOS关键词	INDUCED APOPTOSIS ; NITRIC-OXIDE ; MICROGLIAL ACTIVATION ; DOPAMINERGIC-NEURONS ; INDUCED DEGENERATION ; PARKINSONS-DISEASE ; SUBSTANTIA-NIGRA ; FREE-RADICALS ; PC12 CELLS ; COMPLEX-I
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	PHARMACEUTICAL SOC JAPAN
WOS记录号	WOS:000239542300014
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/273545]
专题	药理学第二研究室
通讯作者	Zhu, Xing-Zu
作者单位	Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Mat Med, Dept Pharmacol, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Zhao, Fei-Li,Hu, Jing-i Hu,Zhu, Xing-Zu. Monocyte-mediated rotenone neurotoxicity towards human neuroblastoma SH-SY5Y: Role of mitogen-activated protein kinases[J]. BIOLOGICAL & PHARMACEUTICAL BULLETIN,2006,29(7):1372-1377.
APA	Zhao, Fei-Li,Hu, Jing-i Hu,&Zhu, Xing-Zu.(2006).Monocyte-mediated rotenone neurotoxicity towards human neuroblastoma SH-SY5Y: Role of mitogen-activated protein kinases.BIOLOGICAL & PHARMACEUTICAL BULLETIN,29(7),1372-1377.
MLA	Zhao, Fei-Li,et al."Monocyte-mediated rotenone neurotoxicity towards human neuroblastoma SH-SY5Y: Role of mitogen-activated protein kinases".BIOLOGICAL & PHARMACEUTICAL BULLETIN 29.7(2006):1372-1377.