Gold nanoparticles induce heme oxygenase-1 expression through Nrf2 activation and Bach1 export in human vascular endothelial cells

Tsung-Hsuan Lai,1–3 Jiunn-Min Shieh,4,5 Chih-Jen Tsou,1 Wen-Bin Wu11School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan; 2Department of Obstetrics and Gynecology, Cathay General Hospital, Taipei, Taiwan; 3Institute of Systems Biology and Bioinformatics, National Central...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Lai TH, Shieh JM, Tsou CJ, Wu WB
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/466ed07aefb845ac8f1f1cb55a9cf0f5
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:466ed07aefb845ac8f1f1cb55a9cf0f5
record_format	dspace
spelling	oai:doaj.org-article:466ed07aefb845ac8f1f1cb55a9cf0f52021-12-02T04:33:03ZGold nanoparticles induce heme oxygenase-1 expression through Nrf2 activation and Bach1 export in human vascular endothelial cells1178-2013https://doaj.org/article/466ed07aefb845ac8f1f1cb55a9cf0f52015-09-01T00:00:00Zhttps://www.dovepress.com/gold-nanoparticles-induce-heme-oxygenase-1-expression-through-nrf2-act-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Tsung-Hsuan Lai,1–3 Jiunn-Min Shieh,4,5 Chih-Jen Tsou,1 Wen-Bin Wu11School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan; 2Department of Obstetrics and Gynecology, Cathay General Hospital, Taipei, Taiwan; 3Institute of Systems Biology and Bioinformatics, National Central University, Jhongli City, Taiwan; 4Department of Internal Medicine, Chi-Mei Medical Center, Tainan, Taiwan; 5Department of Recreation and Healthcare Management, Chia Nan University of Pharmacy and Science, Tainan, TaiwanAbstract: It has been reported that increased levels and activity of the heme oxygenase-1 (HO-1) protein ameliorate tissue injuries. In the present study, we investigated the effects and mechanisms of action of gold nanoparticles (AuNPs) on HO-1 protein expression in human vascular endothelial cells (ECs). The AuNPs induced HO-1 protein and mRNA expression in a concentration- and time-dependent manner. The induction was reduced by the thiol-containing antioxidants, including N-acetylcysteine and glutathione, but not by the non-thiol-containing antioxidants and inhibitors that block the enzymes for intracellular reactive oxygen species generation. The AuNPs enhanced Nrf2 protein levels but did not affect Nrf2 mRNA expression. In response to the AuNP treatment, the cytosolic Nrf2 translocated to the nucleus, and, concomitantly, Bach1 exited the nucleus and its tyrosine phosphorylation increased. The chromatin immunoprecipitation assay revealed that the translocated Nrf2 bound to the antioxidant-response element located in the E2 enhancer region of the HO-1 gene promoter and acted as a transcription factor. Although N-acetylcysteine inhibited the AuNP-induced Nrf2 nuclear translocation, the AuNPs did not promote intracellular reactive oxygen species production or endoplasmic reticulum stress in the ECs. Knockdown of Nrf2 expression by RNA interference significantly inhibited AuNP-induced HO-1 expression at the protein and mRNA levels. In summary, AuNPs enhance the levels and nuclear translocation of the Nrf2 protein and Bach1 export/tyrosine phosphorylation, leading to Nrf2 binding to the HO-1 E2 enhancer promoter region to drive HO-1 expression in ECs. This study, together with our parallel findings, demonstrates that AuNPs can act as an HO-1 inducer, which may partially contribute to their anti-inflammatory bioactivity in human vascular ECs.Keywords: endothelium, inflammation, Keap1, nuclear export, translocation, tyrosine phosphorylationLai THShieh JMTsou CJWu WBDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 5925-5939 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Lai TH Shieh JM Tsou CJ Wu WB Gold nanoparticles induce heme oxygenase-1 expression through Nrf2 activation and Bach1 export in human vascular endothelial cells
description	Tsung-Hsuan Lai,1–3 Jiunn-Min Shieh,4,5 Chih-Jen Tsou,1 Wen-Bin Wu11School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan; 2Department of Obstetrics and Gynecology, Cathay General Hospital, Taipei, Taiwan; 3Institute of Systems Biology and Bioinformatics, National Central University, Jhongli City, Taiwan; 4Department of Internal Medicine, Chi-Mei Medical Center, Tainan, Taiwan; 5Department of Recreation and Healthcare Management, Chia Nan University of Pharmacy and Science, Tainan, TaiwanAbstract: It has been reported that increased levels and activity of the heme oxygenase-1 (HO-1) protein ameliorate tissue injuries. In the present study, we investigated the effects and mechanisms of action of gold nanoparticles (AuNPs) on HO-1 protein expression in human vascular endothelial cells (ECs). The AuNPs induced HO-1 protein and mRNA expression in a concentration- and time-dependent manner. The induction was reduced by the thiol-containing antioxidants, including N-acetylcysteine and glutathione, but not by the non-thiol-containing antioxidants and inhibitors that block the enzymes for intracellular reactive oxygen species generation. The AuNPs enhanced Nrf2 protein levels but did not affect Nrf2 mRNA expression. In response to the AuNP treatment, the cytosolic Nrf2 translocated to the nucleus, and, concomitantly, Bach1 exited the nucleus and its tyrosine phosphorylation increased. The chromatin immunoprecipitation assay revealed that the translocated Nrf2 bound to the antioxidant-response element located in the E2 enhancer region of the HO-1 gene promoter and acted as a transcription factor. Although N-acetylcysteine inhibited the AuNP-induced Nrf2 nuclear translocation, the AuNPs did not promote intracellular reactive oxygen species production or endoplasmic reticulum stress in the ECs. Knockdown of Nrf2 expression by RNA interference significantly inhibited AuNP-induced HO-1 expression at the protein and mRNA levels. In summary, AuNPs enhance the levels and nuclear translocation of the Nrf2 protein and Bach1 export/tyrosine phosphorylation, leading to Nrf2 binding to the HO-1 E2 enhancer promoter region to drive HO-1 expression in ECs. This study, together with our parallel findings, demonstrates that AuNPs can act as an HO-1 inducer, which may partially contribute to their anti-inflammatory bioactivity in human vascular ECs.Keywords: endothelium, inflammation, Keap1, nuclear export, translocation, tyrosine phosphorylation
format	article
author	Lai TH Shieh JM Tsou CJ Wu WB
author_facet	Lai TH Shieh JM Tsou CJ Wu WB
author_sort	Lai TH
title	Gold nanoparticles induce heme oxygenase-1 expression through Nrf2 activation and Bach1 export in human vascular endothelial cells
title_short	Gold nanoparticles induce heme oxygenase-1 expression through Nrf2 activation and Bach1 export in human vascular endothelial cells
title_full	Gold nanoparticles induce heme oxygenase-1 expression through Nrf2 activation and Bach1 export in human vascular endothelial cells
title_fullStr	Gold nanoparticles induce heme oxygenase-1 expression through Nrf2 activation and Bach1 export in human vascular endothelial cells
title_full_unstemmed	Gold nanoparticles induce heme oxygenase-1 expression through Nrf2 activation and Bach1 export in human vascular endothelial cells
title_sort	gold nanoparticles induce heme oxygenase-1 expression through nrf2 activation and bach1 export in human vascular endothelial cells
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/466ed07aefb845ac8f1f1cb55a9cf0f5
work_keys_str_mv	AT laith goldnanoparticlesinducehemeoxygenase1expressionthroughnrf2activationandbach1exportinhumanvascularendothelialcells AT shiehjm goldnanoparticlesinducehemeoxygenase1expressionthroughnrf2activationandbach1exportinhumanvascularendothelialcells AT tsoucj goldnanoparticlesinducehemeoxygenase1expressionthroughnrf2activationandbach1exportinhumanvascularendothelialcells AT wuwb goldnanoparticlesinducehemeoxygenase1expressionthroughnrf2activationandbach1exportinhumanvascularendothelialcells
_version_	1718401180145549312

Gold nanoparticles induce heme oxygenase-1 expression through Nrf2 activation and Bach1 export in human vascular endothelial cells

Ejemplares similares