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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
2006-07-01
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
通讯作者Zhu, xing-zu(xzzhu@mail.shcnc.ac.cn)
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
WOS类目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
URI标识http://www.corc.org.cn/handle/1471x/2375268
专题武汉病毒研究所
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.
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