Hypoxia induces PDK4 gene expression through induction of the orphan nuclear receptor ERRγ.

Multiple cellular signaling pathways that control metabolism and survival are activated when cell are incubated under hypoxic conditions. Activation of the hypoxia inducible factor (HIF)-1 promotes expression of genes that increase the capacity to cope with the stress imposed by a reduced oxygen env...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Ja Hee Lee, Eun-Jin Kim, Don-Kyu Kim, Ji-Min Lee, Seung Bum Park, In-Kyu Lee, Robert A Harris, Mi-Ock Lee, Hueng-Sik Choi
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a110d7abfb5c496dadb89d59f098fd05
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:a110d7abfb5c496dadb89d59f098fd05
record_format	dspace
spelling	oai:doaj.org-article:a110d7abfb5c496dadb89d59f098fd052021-11-18T08:13:59ZHypoxia induces PDK4 gene expression through induction of the orphan nuclear receptor ERRγ.1932-620310.1371/journal.pone.0046324https://doaj.org/article/a110d7abfb5c496dadb89d59f098fd052012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23050013/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Multiple cellular signaling pathways that control metabolism and survival are activated when cell are incubated under hypoxic conditions. Activation of the hypoxia inducible factor (HIF)-1 promotes expression of genes that increase the capacity to cope with the stress imposed by a reduced oxygen environment. Here we show that the orphan nuclear receptor estrogen related receptor γ (ERRγ) plays a critical role in hypoxia-mediated activation of pyruvate dehydrogenase kinase 4 (PDK4) gene expression. ERRγ mRNA and protein levels were increased by hypoxia or desferrioxamine (DFO) treatment in hepatoma cell lines. Co-expression of HIF-1α and β increased ERRγ promoter activity as well as mRNA expression, while knockdown of endogenous HIF-1α reduced the hypoxia-mediated induction of ERRγ. In addition, hypoxia also increased the promoter activity and mRNA level of PDK4 in HepG2 cells. Adenovirus mediated-overexpression of ERRγ specifically increased PDK4 gene expression, while ablation of endogenous ERRγ significantly decreased hypoxia-mediated induction of PDK4 gene expression. Finally, GSK5182, an inverse agonist of ERRγ, strongly inhibited the hypoxia-mediated induction of PDK4 protein and promoter activity. Regulation of the transcriptional activity of ERRγ may provide a therapeutic approach for the regulation of PDK4 gene expression under hypoxia.Ja Hee LeeEun-Jin KimDon-Kyu KimJi-Min LeeSeung Bum ParkIn-Kyu LeeRobert A HarrisMi-Ock LeeHueng-Sik ChoiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 9, p e46324 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ja Hee Lee Eun-Jin Kim Don-Kyu Kim Ji-Min Lee Seung Bum Park In-Kyu Lee Robert A Harris Mi-Ock Lee Hueng-Sik Choi Hypoxia induces PDK4 gene expression through induction of the orphan nuclear receptor ERRγ.
description	Multiple cellular signaling pathways that control metabolism and survival are activated when cell are incubated under hypoxic conditions. Activation of the hypoxia inducible factor (HIF)-1 promotes expression of genes that increase the capacity to cope with the stress imposed by a reduced oxygen environment. Here we show that the orphan nuclear receptor estrogen related receptor γ (ERRγ) plays a critical role in hypoxia-mediated activation of pyruvate dehydrogenase kinase 4 (PDK4) gene expression. ERRγ mRNA and protein levels were increased by hypoxia or desferrioxamine (DFO) treatment in hepatoma cell lines. Co-expression of HIF-1α and β increased ERRγ promoter activity as well as mRNA expression, while knockdown of endogenous HIF-1α reduced the hypoxia-mediated induction of ERRγ. In addition, hypoxia also increased the promoter activity and mRNA level of PDK4 in HepG2 cells. Adenovirus mediated-overexpression of ERRγ specifically increased PDK4 gene expression, while ablation of endogenous ERRγ significantly decreased hypoxia-mediated induction of PDK4 gene expression. Finally, GSK5182, an inverse agonist of ERRγ, strongly inhibited the hypoxia-mediated induction of PDK4 protein and promoter activity. Regulation of the transcriptional activity of ERRγ may provide a therapeutic approach for the regulation of PDK4 gene expression under hypoxia.
format	article
author	Ja Hee Lee Eun-Jin Kim Don-Kyu Kim Ji-Min Lee Seung Bum Park In-Kyu Lee Robert A Harris Mi-Ock Lee Hueng-Sik Choi
author_facet	Ja Hee Lee Eun-Jin Kim Don-Kyu Kim Ji-Min Lee Seung Bum Park In-Kyu Lee Robert A Harris Mi-Ock Lee Hueng-Sik Choi
author_sort	Ja Hee Lee
title	Hypoxia induces PDK4 gene expression through induction of the orphan nuclear receptor ERRγ.
title_short	Hypoxia induces PDK4 gene expression through induction of the orphan nuclear receptor ERRγ.
title_full	Hypoxia induces PDK4 gene expression through induction of the orphan nuclear receptor ERRγ.
title_fullStr	Hypoxia induces PDK4 gene expression through induction of the orphan nuclear receptor ERRγ.
title_full_unstemmed	Hypoxia induces PDK4 gene expression through induction of the orphan nuclear receptor ERRγ.
title_sort	hypoxia induces pdk4 gene expression through induction of the orphan nuclear receptor errγ.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/a110d7abfb5c496dadb89d59f098fd05
work_keys_str_mv	AT jaheelee hypoxiainducespdk4geneexpressionthroughinductionoftheorphannuclearreceptorerrg AT eunjinkim hypoxiainducespdk4geneexpressionthroughinductionoftheorphannuclearreceptorerrg AT donkyukim hypoxiainducespdk4geneexpressionthroughinductionoftheorphannuclearreceptorerrg AT jiminlee hypoxiainducespdk4geneexpressionthroughinductionoftheorphannuclearreceptorerrg AT seungbumpark hypoxiainducespdk4geneexpressionthroughinductionoftheorphannuclearreceptorerrg AT inkyulee hypoxiainducespdk4geneexpressionthroughinductionoftheorphannuclearreceptorerrg AT robertaharris hypoxiainducespdk4geneexpressionthroughinductionoftheorphannuclearreceptorerrg AT miocklee hypoxiainducespdk4geneexpressionthroughinductionoftheorphannuclearreceptorerrg AT huengsikchoi hypoxiainducespdk4geneexpressionthroughinductionoftheorphannuclearreceptorerrg
_version_	1718422062803976192

Hypoxia induces PDK4 gene expression through induction of the orphan nuclear receptor ERRγ.

Ejemplares similares