کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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6265250 | 1614069 | 2011 | 11 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Research ReportProtective effects of statins on l-DOPA neurotoxicity due to the activation of phosphatidylinositol 3-kinase and free radical scavenging in PC12 cell culture Research ReportProtective effects of statins on l-DOPA neurotoxicity due to the activation of phosphatidylinositol 3-kinase and free radical scavenging in PC12 cell culture](/preview/png/6265250.png)
Neurotoxic effects have been suggested for l-3,4-dihydroxyphenylalanine (l-DOPA), while neuroprotective effects have been proposed for statins. We investigated whether certain statins (simvastatin or pitavastatin) could inhibit l-DOPA neurotoxicity. Neuronally-differentiated PC12 (nPC12) cells were treated with l-DOPA and/or statins for 24 h, and their viabilities were measured using a cell counting kit, trypan blue staining, and 4â²,6-diamidino-2-phenylindole (DAPI) staining. Free radical and specific intracellular signaling protein levels were measured with 2â²,7â²-dichlorodihydrofluorescein diacetate (DCFH-DA) and Western blotting, respectively. High concentrations of l-DOPA reduced nPC12 cell viability, but combined treatment with statins restored viability. Treatment with 200 μM l-DOPA increased free radical and hydroxyl radical levels, but combined treatment with 5 μM statins decreased these levels. Survival-related signaling proteins were decreased in nPC12 cells treated with 200 μM l-DOPA, but combined treatment with 5 μM statins significantly increased the levels of these proteins. Treatment with 200 μM l-DOPA significantly increased death-related signaling proteins, while combined treatment with 5 μM statins reduced the levels of these proteins. Pretreatment with LY294002, a phosphatidylinositol 3 kinase (PI3K) inhibitor, before combined treatment with statins and l-DOPA almost completely blocked the protective effects of statins. These results indicate that statins reduce l-DOPA neurotoxicity by lowering oxidative stress and by enhancing survival signals and inhibiting death signals via activation of the PI3K pathway.
Research HighlightsâºL-DOPA produces neurotoxicity at high concentration. âºStatins prevent l-DOPA neurotoxicity. âºStatins' neuroprotective effects are associated with the activation of the PI3K pathway. âºAntioxidant effects of statins are also related to the protective effects against l-DOPA neurotoxicity.
Journal: Brain Research - Volume 1370, 25 January 2011, Pages 53-63