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Atorvastatin attenuates mitochondrial toxin-induced striatal degeneration, with decreasing iNOS/c-Jun levels and activating ERK/Akt pathways
DC Field | Value | Language |
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dc.contributor.author | Lee, S. T. | - |
dc.contributor.author | Chu, K. | - |
dc.contributor.author | Park, J. E. | - |
dc.contributor.author | Hong, N. H. | - |
dc.contributor.author | Im, W. S. | - |
dc.contributor.author | Kang, L. | - |
dc.contributor.author | Han, Z. | - |
dc.contributor.author | Jung, K. H. | - |
dc.contributor.author | Kim, M. W. | - |
dc.contributor.author | Kim, M. | - |
dc.date.accessioned | 2009-12-24T07:35:35Z | - |
dc.date.available | 2009-12-24T07:35:35Z | - |
dc.date.issued | 2007-11-03 | - |
dc.identifier.citation | J Neurochem. 2008 Mar;104(5):1190-200. Epub 2007 Nov 1. | en |
dc.identifier.issn | 1471-4159 (Electronic) | - |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17976163 | - |
dc.identifier.uri | https://hdl.handle.net/10371/22333 | - |
dc.description.abstract | Mitochondrial dysfunction is a major contributor to neurodegeneration, and causes vulnerability to oxidative stress and the activations of downstream cell death pathways. 3-Hydroxy-3-methyl-glutaryl-CoA reductase inhibitors, statins, were originally developed as cholesterol lowering agents, and have cholesterol-independent anti-excitotoxic and anti-oxidative properties. We investigated whether atorvastatin can prevent the neurodegeneration induced by a mitochondrial toxin, 3-nitropropionic acid (3NP), which inhibits succinate dehydrogenase complex II. Male Lewis rats were administered 3NP (63 mg/kg/day) using osmotic pumps for 5 days to induce striatal degeneration, and were also treated with either atorvastatin (1 or 10 mg/kg/day, orally) or vehicle (control) on five consecutive days. Atorvastatin-treated rats showed fewer neurologic deficits than control animals as measured at day 3-5. Atorvastatin-treated animals showed reduced striatal lesion volumes by Nissl staining, and decreased numbers of TUNEL-positive apoptosis and Fluoro-Jade C-positive degenerating neurons at 5 days. Atorvastatin reduced the numbers of c-Jun-positive and p-c-Jun-positive cells, as well as 3-nitrotyrosin-positive cells. In addition, atorvastatin increased p-extracellular signal-regulated kinase and p-Akt levels, and attenuated the up-regulation of inducible nitric oxide synthase by 3NP. When N(omega)-nitro-l-arginine methyl ester hydrochloride was administered concomitantly with the 3NP infusion, atorvastatin failed to further reduce the striatal lesion volume and c-Jun levels compared to the vehicle treatment. In summary, atorvastatin decreased striatal neurodegeneration induced by 3NP, with attenuating inducible nitric oxide synthase and c-Jun levels as well as activating extracellular signal-regulated kinase and Akt. | en |
dc.language.iso | en | - |
dc.publisher | Wiley-Blackwell | en |
dc.subject | Animals | en |
dc.subject | Corpus Striatum/drug effects/enzymology | en |
dc.subject | Disease Models, Animal | en |
dc.subject | Enzyme Activation/drug effects/physiology | en |
dc.subject | Extracellular Signal-Regulated MAP Kinases/*metabolism | en |
dc.subject | Heptanoic Acids/*pharmacology/therapeutic use | en |
dc.subject | JNK Mitogen-Activated Protein Kinases/antagonists & inhibitors/*metabolism | en |
dc.subject | MAP Kinase Signaling System/drug effects/physiology | en |
dc.subject | Male | en |
dc.subject | Mitochondria/*drug effects/enzymology | en |
dc.subject | Nerve Degeneration/*enzymology/prevention & control | en |
dc.subject | Neurotoxins/toxicity | en |
dc.subject | Nitric Oxide Synthase Type II/antagonists & inhibitors/*metabolism | en |
dc.subject | Nitro Compounds/*toxicity | en |
dc.subject | Propionic Acids/*toxicity | en |
dc.subject | Protein Kinase Inhibitors/pharmacology | en |
dc.subject | Proto-Oncogene Proteins c-akt/*metabolism | en |
dc.subject | Pyrroles/*pharmacology/therapeutic use | en |
dc.subject | Rats | en |
dc.subject | Rats, Inbred Lew | en |
dc.subject | Rats, Sprague-Dawley | en |
dc.title | Atorvastatin attenuates mitochondrial toxin-induced striatal degeneration, with decreasing iNOS/c-Jun levels and activating ERK/Akt pathways | en |
dc.type | Article | en |
dc.contributor.AlternativeAuthor | 이순태 | - |
dc.contributor.AlternativeAuthor | 주건 | - |
dc.contributor.AlternativeAuthor | 박정은 | - |
dc.contributor.AlternativeAuthor | 홍난형 | - |
dc.contributor.AlternativeAuthor | 임우석 | - |
dc.contributor.AlternativeAuthor | 강라미 | - |
dc.contributor.AlternativeAuthor | 정건화 | - |
dc.contributor.AlternativeAuthor | 김민욱 | - |
dc.contributor.AlternativeAuthor | 김만호 | - |
dc.identifier.doi | 10.1111/j.1471-4159.2007.05044.x | - |
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