Monocyte-Mediated Rotenone Neurotoxicity towards Human Neuroblastoma SH-SY5Y : Role of Mitogen-Activated Protein Kinases(Pharmacology)

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概要

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• 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 6.25-50nM, 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 48h. 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 SH-SY5Y 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 50nM, the percentage of apoptotic SH-SY5Y cells accumulated to 31.5% and 37.0% respectively. We further investigated whether rotenone (50nM) 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.

• 社団法人日本薬学会の論文
• 2006-07-01

著者

• Hu Jing-hui

  Department Of Pharmacology Institute Of Materia Medica Shanghai Institutes For Biological Sciences C

• ZHAO Fei-Li

  Department of Pharmacology, Institute of Materia Medica, Shanghai Institutes for Biological Sciences

• ZHU Xing-Zu

  Department of Pharmacology, Institute of Materia Medica, Shanghai Institutes for Biological Sciences

• Zhao Fei-li

  Department Of Pharmacology Institute Of Materia Medica Shanghai Institutes For Biological Sciences C

• Zhu Xing-zu

  Department Of Pharmacology Institute Of Materia Medica Shanghai Institutes For Biological Sciences C

関連論文

• Monocyte-Mediated Rotenone Neurotoxicity towards Human Neuroblastoma SH-SY5Y : Role of Mitogen-Activated Protein Kinases(Pharmacology)
• Potentiation of Adenosine A_1 Receptor Agonist CPA-Induced Antinociception by Paeoniflorin in Mice(Pharmacology)

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