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Transcriptional Activation of Low-Density Lipoprotein Receptor Gene by DJ-1 and Effect of DJ-1 on Cholesterol Homeostasis
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| Title: | Transcriptional Activation of Low-Density Lipoprotein Receptor Gene by DJ-1 and Effect of DJ-1 on Cholesterol Homeostasis |
| Authors: | Yamaguchi, Shiori Browse this author | | Yamane, Takuya Browse this author | | Takahashi-Niki, Kazuko Browse this author →KAKEN DB | | Kato, Izumi Browse this author | | Niki, Takeshi Browse this author →KAKEN DB | | Goldberg, Matthew S. Browse this author | | Shen, Jie Browse this author | | Ishimoto, Kenji Browse this author | | Doi, Takefumi Browse this author →KAKEN DB | | Iguchi-Ariga, Sanae M. M. Browse this author →KAKEN DB | | Ariga, Hiroyoshi Browse this author →KAKEN DB |
| Issue Date: | 30-May-2012 |
| Publisher: | Public Library of Science |
| Journal Title: | PLoS One |
| Volume: | 7 |
| Issue: | 5 |
| Start Page: | e38144 |
| Publisher DOI: | 10.1371/journal.pone.0038144 |
| Abstract: | DJ-1 is a novel oncogene and also causative gene for familial Parkinson's disease park7. DJ-1 has multiple functions that include transcriptional regulation, anti-oxidative reaction and chaperone and mitochondrial regulation. For transcriptional regulation, DJ-1 acts as a coactivator that binds to various transcription factors, resulting in stimulation or repression of the expression of their target genes. In this study, we found the low-density lipoprotein receptor (LDLR) gene is a transcriptional target gene for DJ-1. Reduced expression of LDLR mRNA and protein was observed in DJ-1-knockdown cells and DJ-1-knockout mice and this occurred at the transcription level. Reporter gene assays using various deletion and point mutations of the LDLR promoter showed that DJ-1 stimulated promoter activity by binding to the sterol regulatory element (SRE) with sterol regulatory element binding protein (SREBP) and that stimulating activity of DJ-1 toward LDLR promoter activity was enhanced by oxidation of DJ-1. Chromatin immunoprecipitation, gel-mobility shift and co-immunoprecipitation assays showed that DJ-1 made a complex with SREBP on the SRE. Furthermore, it was found that serum LDL cholesterol level was increased in DJ-1-knockout male, but not female, mice and that the increased serum LDL cholesterol level in DJ-1-knockout male mice was cancelled by administration with estrogen, suggesting that estrogen compensates the increased level of serum LDL cholesterol in DJ-1-knockout female mice. This is the first report that DJ-1 participates in metabolism of fatty acid synthesis through transcriptional regulation of the LDLR gene. |
| Rights: | http://creativecommons.org/licenses/by/3.0/ |
| Type: | article |
| URI: | http://hdl.handle.net/2115/49574 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 有賀 寛芳
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