Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 안주홍 | - |
dc.date.accessioned | 2018-03-13T00:14:48Z | - |
dc.date.available | 2018-03-13T00:14:48Z | - |
dc.date.issued | 2013-06 | - |
dc.identifier.citation | PLoS ONE, 10 June 2013, 8(6), pp.e64953 | en_US |
dc.identifier.issn | 1932-6203 | - |
dc.identifier.uri | http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0064953 | - |
dc.identifier.uri | http://hdl.handle.net/20.500.11754/45625 | - |
dc.description.abstract | Intracellular accumulation of polyglutamine (polyQ)-expanded Huntingtin (Htt) protein is a hallmark of Huntington's disease (HD). This study evaluated whether activation of Sirt1 by the anti-cancer agent, beta-lapachone (beta-lap), induces autophagy in human neuroblastoma SH-SY5Y cells, thereby reducing intracellular levels of polyQ aggregates and their concomitant cytotoxicity. Treatment of cells with beta-lap markedly diminished the cytotoxicity induced by forced expression of Htt exon 1 containing a pathogenic polyQ stretch fused to green fluorescent protein (HttEx1(97Q)-GFP). beta-lap increased autophagy in SH-SY5Y cells, as evidenced by the increased formation of LC3-II and autolysosomes. Furthermore, beta-lap reduced HttEx1(97Q)-GFP aggregation, which was significantly prevented by co-incubation with 3-methyladenine, an inhibitor of autophagy. beta-lap increased Sirt1 activity, as shown by the increased deacetylation of the Sirt1 substrates, PARP-1 and Atg5, and the nuclear translocation of FOXO1. Both the induction of autophagy and attenuation of HttEx1(97Q)-GFP aggregation by beta-lap were significantly prevented by co-incubation with sirtinol, a general sirtuin inhibitor or by co-transfection with shRNA against Sirt1. The pro-autophagic actions of beta-lap were further investigated in a transgenic Caenorhabditis elegans (C. elegans) line that expressed Q67 fused to cyanine fluorescent protein (Q67). Notably, beta-lap reduced the number of Q67 puncta and restored Q67-induced defects in motility, which were largely prevented by pre-treatment with RNAi against sir-2.1, the C. elegans orthologue of Sirt1. Collectively, these data suggest that beta-lap induces autophagy through activation of Sirt1, which in turn leads to a reduction in polyQ aggregation and cellular toxicity. Thus, beta-lap provides a novel therapeutic opportunity for the treatment of HD. | en_US |
dc.language.iso | en | en_US |
dc.publisher | PUBLIC LIBRARY SCIENCE | en_US |
dc.subject | BREAST-CANCER CELLS | en_US |
dc.subject | BETA-LAPACHONE | en_US |
dc.subject | HUNTINGTONS-DISEASE | en_US |
dc.subject | CAENORHABDITIS-ELEGANS | en_US |
dc.subject | MUTANT HUNTINGTIN | en_US |
dc.subject | INTRANUCLEAR INCLUSIONS | en_US |
dc.subject | MOUSE MODELS | en_US |
dc.subject | APOPTOSIS | en_US |
dc.subject | AGGREGATION | en_US |
dc.subject | INDUCTION | en_US |
dc.title | Pharmacological Activation of Sirt1 Ameliorates Polyglutamine-Induced Toxicity through the Regulation of Autophagy | en_US |
dc.type | Article | en_US |
dc.relation.no | 6 | - |
dc.relation.volume | 8 | - |
dc.identifier.doi | 10.1371/journal.pone.0064953 | - |
dc.relation.page | 1-1 | - |
dc.relation.journal | PLOS ONE | - |
dc.contributor.googleauthor | Shin, B.H. | - |
dc.contributor.googleauthor | Park, S.M | - |
dc.contributor.googleauthor | Park, W.J. | - |
dc.contributor.googleauthor | Lim, Y | - |
dc.contributor.googleauthor | Oh, H.J. | - |
dc.contributor.googleauthor | Kim, D.H | - |
dc.contributor.googleauthor | Song, W.K | - |
dc.contributor.googleauthor | Lee, S.-K | - |
dc.contributor.googleauthor | Ahnn, J. | - |
dc.contributor.googleauthor | Kwak, T. | - |
dc.relation.code | 2013007124 | - |
dc.sector.campus | S | - |
dc.sector.daehak | COLLEGE OF NATURAL SCIENCES[S] | - |
dc.sector.department | DEPARTMENT OF LIFE SCIENCE | - |
dc.identifier.pid | joohong | - |
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