Involvement of PINK1/parkin-mediated mitophagy in ZnO nanoparticle-induced toxicity in BV-2 cells

Limin Wei,1,2,* Jianfeng Wang,1,2,* Aijie Chen,1 Jia Liu,1 Xiaoli Feng,1 Longquan Shao1 1Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Pediatric Dentistry, School and Hospital of Stomatology, Wenzhou Medical...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Wei L, Wang J, Chen A, Liu J, Feng X, Shao L
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	PINK1/parkin Mitophagy Autophagy Zinc oxide nanoparticles Neurotoxicity Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/dd25ac0362e04dc2900d9ac73bfdcb3b
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:dd25ac0362e04dc2900d9ac73bfdcb3b
record_format	dspace
spelling	oai:doaj.org-article:dd25ac0362e04dc2900d9ac73bfdcb3b2021-12-02T07:45:07ZInvolvement of PINK1/parkin-mediated mitophagy in ZnO nanoparticle-induced toxicity in BV-2 cells1178-2013https://doaj.org/article/dd25ac0362e04dc2900d9ac73bfdcb3b2017-03-01T00:00:00Zhttps://www.dovepress.com/involvement-of-pink1parkin-mediated-mitophagy-in-zno-nanoparticle-indu-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Limin Wei,1,2,* Jianfeng Wang,1,2,* Aijie Chen,1 Jia Liu,1 Xiaoli Feng,1 Longquan Shao1 1Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Pediatric Dentistry, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, People’s Republic of China *These authors contributed equally to this work Abstract: With the increasing application of zinc oxide nanoparticles (ZnO NPs) in biological materials, the neurotoxicity caused by these particles has raised serious concerns. However, the underlying molecular mechanisms of the toxic effect of ZnO NPs on brain cells remain unclear. Mitochondrial damage has been reported to be a factor in the toxicity of ZnO NPs. PINK1/parkin-mediated mitophagy is a newly emerging additional function of autophagy that selectively degrades impaired mitochondria. Here, a PINK1 gene knockdown BV-2 cell model was established to determine whether PINK1/parkin-mediated mitophagy was involved in ZnO NP-induced toxicity in BV-2 cells. The expression of total parkin, mito-parkin, cyto-parkin, and PINK1 both in wild type and PINK1-/- BV-2 cells was evaluated using Western blot analysis after the cells were exposed to 10 µg/mL of 50 nm ZnO NPs for 2, 4, 8, 12, and 24 h. The findings suggested that the downregulation of PINK1 resulted in a significant reduction in the survival rate after ZnO NP exposure compared with that of control cells. ZnO NPs were found to induce the transportation of parkin from the cytoplasm to the mitochondria, implying the involvement of mitophagy in ZnO NP-induced toxicity. The deletion of the PINK1 gene inhibited the recruitment of parkin to the mitochondria, causing failure of the cell to trigger mitophagy. The present study demonstrated that apart from autophagy, PINK1/parkin-mediated mitophagy plays a protective role in ZnO NP-induced cytotoxicity. Keywords: PINK1/parkin, mitophagy, autophagy, zinc oxide nanoparticles neurotoxicityWei LWang JChen ALiu JFeng XShao LDove Medical PressarticlePINK1/parkinMitophagyAutophagyZinc oxide nanoparticlesNeurotoxicityMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 1891-1903 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	PINK1/parkin Mitophagy Autophagy Zinc oxide nanoparticles Neurotoxicity Medicine (General) R5-920
spellingShingle	PINK1/parkin Mitophagy Autophagy Zinc oxide nanoparticles Neurotoxicity Medicine (General) R5-920 Wei L Wang J Chen A Liu J Feng X Shao L Involvement of PINK1/parkin-mediated mitophagy in ZnO nanoparticle-induced toxicity in BV-2 cells
description	Limin Wei,1,2,* Jianfeng Wang,1,2,* Aijie Chen,1 Jia Liu,1 Xiaoli Feng,1 Longquan Shao1 1Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Pediatric Dentistry, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, People’s Republic of China *These authors contributed equally to this work Abstract: With the increasing application of zinc oxide nanoparticles (ZnO NPs) in biological materials, the neurotoxicity caused by these particles has raised serious concerns. However, the underlying molecular mechanisms of the toxic effect of ZnO NPs on brain cells remain unclear. Mitochondrial damage has been reported to be a factor in the toxicity of ZnO NPs. PINK1/parkin-mediated mitophagy is a newly emerging additional function of autophagy that selectively degrades impaired mitochondria. Here, a PINK1 gene knockdown BV-2 cell model was established to determine whether PINK1/parkin-mediated mitophagy was involved in ZnO NP-induced toxicity in BV-2 cells. The expression of total parkin, mito-parkin, cyto-parkin, and PINK1 both in wild type and PINK1-/- BV-2 cells was evaluated using Western blot analysis after the cells were exposed to 10 µg/mL of 50 nm ZnO NPs for 2, 4, 8, 12, and 24 h. The findings suggested that the downregulation of PINK1 resulted in a significant reduction in the survival rate after ZnO NP exposure compared with that of control cells. ZnO NPs were found to induce the transportation of parkin from the cytoplasm to the mitochondria, implying the involvement of mitophagy in ZnO NP-induced toxicity. The deletion of the PINK1 gene inhibited the recruitment of parkin to the mitochondria, causing failure of the cell to trigger mitophagy. The present study demonstrated that apart from autophagy, PINK1/parkin-mediated mitophagy plays a protective role in ZnO NP-induced cytotoxicity. Keywords: PINK1/parkin, mitophagy, autophagy, zinc oxide nanoparticles neurotoxicity
format	article
author	Wei L Wang J Chen A Liu J Feng X Shao L
author_facet	Wei L Wang J Chen A Liu J Feng X Shao L
author_sort	Wei L
title	Involvement of PINK1/parkin-mediated mitophagy in ZnO nanoparticle-induced toxicity in BV-2 cells
title_short	Involvement of PINK1/parkin-mediated mitophagy in ZnO nanoparticle-induced toxicity in BV-2 cells
title_full	Involvement of PINK1/parkin-mediated mitophagy in ZnO nanoparticle-induced toxicity in BV-2 cells
title_fullStr	Involvement of PINK1/parkin-mediated mitophagy in ZnO nanoparticle-induced toxicity in BV-2 cells
title_full_unstemmed	Involvement of PINK1/parkin-mediated mitophagy in ZnO nanoparticle-induced toxicity in BV-2 cells
title_sort	involvement of pink1/parkin-mediated mitophagy in zno nanoparticle-induced toxicity in bv-2 cells
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/dd25ac0362e04dc2900d9ac73bfdcb3b
work_keys_str_mv	AT weil involvementofpink1parkinmediatedmitophagyinznonanoparticleinducedtoxicityinbv2cells AT wangj involvementofpink1parkinmediatedmitophagyinznonanoparticleinducedtoxicityinbv2cells AT chena involvementofpink1parkinmediatedmitophagyinznonanoparticleinducedtoxicityinbv2cells AT liuj involvementofpink1parkinmediatedmitophagyinznonanoparticleinducedtoxicityinbv2cells AT fengx involvementofpink1parkinmediatedmitophagyinznonanoparticleinducedtoxicityinbv2cells AT shaol involvementofpink1parkinmediatedmitophagyinznonanoparticleinducedtoxicityinbv2cells
_version_	1718399251444137984

Involvement of PINK1/parkin-mediated mitophagy in ZnO nanoparticle-induced toxicity in BV-2 cells

Ejemplares similares