Dexamethasone induces the expression of LRRK2 and α-synuclein, two genes that when mutated cause Parkinson’s disease in an autosomal dominant manner
LRRK2 (leucine-rich repeat kinase 2) has been identified as agene corresponding to PARK8, an autosomal-dominant genefor familial Parkinson’s disease (PD). LRRK2 pathogenicspecificmutants induce neurotoxicity and shorten neurites. Toelucidate the mechanism underlying LRRK2 expression, weconstructed t...
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| Format: | Article |
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Korean Society for Biochemistry and Molecular Biology
2013-09-01
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| Series: | BMB Reports |
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| Online Access: | http://bmbreports.org/jbmb/pdf.php?data=MTMxMDA3MTZAcGRmX3JhaW50cmFjZV9sZWV5c0AlNUI0Ni05JTVEMTMwOTI2MTcyN18lMjg0NTQtNDU5JTI5Qk1CXzEyLTIzNC5wZGY= |
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| author | Ji-Min Park Dong-Hwan Ho Hye Jin Yun Hye-Jung Kim Chan Hong Lee Sung Woo Park Young Hoon Kim Ilhong Son Wongi Seol |
| author_facet | Ji-Min Park Dong-Hwan Ho Hye Jin Yun Hye-Jung Kim Chan Hong Lee Sung Woo Park Young Hoon Kim Ilhong Son Wongi Seol |
| author_sort | Ji-Min Park |
| collection | DOAJ |
| description | LRRK2 (leucine-rich repeat kinase 2) has been identified as agene corresponding to PARK8, an autosomal-dominant genefor familial Parkinson’s disease (PD). LRRK2 pathogenicspecificmutants induce neurotoxicity and shorten neurites. Toelucidate the mechanism underlying LRRK2 expression, weconstructed the LRRK2-promoter-luciferase reporter and used itfor promoter analysis. We found that the glucocorticoid receptor(GR) transactivated LRRK2 in a ligand-dependent manner.Using quantitative RT-PCR and Western analysis, we furthershowed that treatment with dexamethasone, a synthetic GRligand, induced LRRK2 expression at both the transcriptionaland translational levels, in dopaminergic MN9D cells. Dexamethasonetreatment also increased expression of α-synuclein,another PD causative gene, and enhanced transactivation ofthe α-synuclein promoter-luciferase reporter. In addition, dexamethasonetreatment to MN9D cells weakly induced cytotoxicitybased on an LDH assay. Because glucocorticoidhormones are secreted in response to stress, our data suggestthat stress might be a related factor in the pathogenesis of PD.[BMB Reports 2013; 46(9): 454-459] |
| first_indexed | 2024-12-10T03:52:40Z |
| format | Article |
| id | doaj.art-9b737c6635f04905a76110a6394687fd |
| institution | Directory Open Access Journal |
| issn | 1976-6696 1976-670X |
| language | English |
| last_indexed | 2024-12-10T03:52:40Z |
| publishDate | 2013-09-01 |
| publisher | Korean Society for Biochemistry and Molecular Biology |
| record_format | Article |
| series | BMB Reports |
| spelling | doaj.art-9b737c6635f04905a76110a6394687fd2022-12-22T02:03:12ZengKorean Society for Biochemistry and Molecular BiologyBMB Reports1976-66961976-670X2013-09-01469454459http://dx.doi.org/10.5483/BMBRep.2013.46.9.234Dexamethasone induces the expression of LRRK2 and α-synuclein, two genes that when mutated cause Parkinson’s disease in an autosomal dominant mannerJi-Min ParkDong-Hwan HoHye Jin YunHye-Jung KimChan Hong LeeSung Woo ParkYoung Hoon KimIlhong SonWongi SeolLRRK2 (leucine-rich repeat kinase 2) has been identified as agene corresponding to PARK8, an autosomal-dominant genefor familial Parkinson’s disease (PD). LRRK2 pathogenicspecificmutants induce neurotoxicity and shorten neurites. Toelucidate the mechanism underlying LRRK2 expression, weconstructed the LRRK2-promoter-luciferase reporter and used itfor promoter analysis. We found that the glucocorticoid receptor(GR) transactivated LRRK2 in a ligand-dependent manner.Using quantitative RT-PCR and Western analysis, we furthershowed that treatment with dexamethasone, a synthetic GRligand, induced LRRK2 expression at both the transcriptionaland translational levels, in dopaminergic MN9D cells. Dexamethasonetreatment also increased expression of α-synuclein,another PD causative gene, and enhanced transactivation ofthe α-synuclein promoter-luciferase reporter. In addition, dexamethasonetreatment to MN9D cells weakly induced cytotoxicitybased on an LDH assay. Because glucocorticoidhormones are secreted in response to stress, our data suggestthat stress might be a related factor in the pathogenesis of PD.[BMB Reports 2013; 46(9): 454-459]http://bmbreports.org/jbmb/pdf.php?data=MTMxMDA3MTZAcGRmX3JhaW50cmFjZV9sZWV5c0AlNUI0Ni05JTVEMTMwOTI2MTcyN18lMjg0NTQtNDU5JTI5Qk1CXzEyLTIzNC5wZGY=α-SynucleinDexamethasoneGlucocorticoid receptor(GR)LRRK2Parkinson’s disease |
| spellingShingle | Ji-Min Park Dong-Hwan Ho Hye Jin Yun Hye-Jung Kim Chan Hong Lee Sung Woo Park Young Hoon Kim Ilhong Son Wongi Seol Dexamethasone induces the expression of LRRK2 and α-synuclein, two genes that when mutated cause Parkinson’s disease in an autosomal dominant manner BMB Reports α-Synuclein Dexamethasone Glucocorticoid receptor(GR) LRRK2 Parkinson’s disease |
| title | Dexamethasone induces the expression of LRRK2 and α-synuclein, two genes that when mutated cause Parkinson’s disease in an autosomal dominant manner |
| title_full | Dexamethasone induces the expression of LRRK2 and α-synuclein, two genes that when mutated cause Parkinson’s disease in an autosomal dominant manner |
| title_fullStr | Dexamethasone induces the expression of LRRK2 and α-synuclein, two genes that when mutated cause Parkinson’s disease in an autosomal dominant manner |
| title_full_unstemmed | Dexamethasone induces the expression of LRRK2 and α-synuclein, two genes that when mutated cause Parkinson’s disease in an autosomal dominant manner |
| title_short | Dexamethasone induces the expression of LRRK2 and α-synuclein, two genes that when mutated cause Parkinson’s disease in an autosomal dominant manner |
| title_sort | dexamethasone induces the expression of lrrk2 and α synuclein two genes that when mutated cause parkinson s disease in an autosomal dominant manner |
| topic | α-Synuclein Dexamethasone Glucocorticoid receptor(GR) LRRK2 Parkinson’s disease |
| url | http://bmbreports.org/jbmb/pdf.php?data=MTMxMDA3MTZAcGRmX3JhaW50cmFjZV9sZWV5c0AlNUI0Ni05JTVEMTMwOTI2MTcyN18lMjg0NTQtNDU5JTI5Qk1CXzEyLTIzNC5wZGY= |
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