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Protective effects of statins on L-DOPA neurotoxicity due to the activation of phosphatidylinositol 3-kinase and free radical scavenging in PC12 cell culture

Title
Protective effects of statins on L-DOPA neurotoxicity due to the activation of phosphatidylinositol 3-kinase and free radical scavenging in PC12 cell culture
Author
이규용
Keywords
L-DOPA; Statin; Phosphatidylinositol 3-kinase; Neurotoxicity
Issue Date
2011-01
Publisher
ELSEVIER SCIENCE BV, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
Citation
Brain research, Vol.1370 No.- [2011], 53-63
Abstract
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 4',6-diamidino-2-phenylindole (DAPI) staining. Free radical and specific intracellular signaling protein levels were measured with 2',7'-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 mu M L-DOPA increased free radical and hydroxyl radical levels, but combined treatment with 5 mu M statins decreased these levels. Survival-related signaling proteins were decreased in nPC12 cells treated with 200 mu M L-DOPA, but combined treatment with 5 mu M statins significantly increased the levels of these proteins. Treatment with 200 mu M L-DOPA significantly increased death-related signaling proteins, while combined treatment with 5 mu M 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. (C) 2010 Elsevier B.V. All rights reserved.
URI
https://www.sciencedirect.com/science/article/pii/S0006899310025345?via%3Dihubhttp://hdl.handle.net/20.500.11754/67098
ISSN
0006-8993
DOI
10.1016/j.brainres.2010.11.021
Appears in Collections:
COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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