Zinc transporter 8 (ZnT8) expression is reduced by ischemic insults: a potential therapeutic target to prevent ischemic retinopathy.

The zinc (Zn(++)) transporter ZnT8 plays a crucial role in zinc homeostasis. It's been reported that an acute decrease in ZnT8 levels impairs β cell function and Zn(++) homeostasis, which contribute to the pathophysiology of diabetes mellitus (DM). Although ZnT8 expression has been detected in...

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Autores principales:	Michael Deniro, Futwan A Al-Mohanna
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/15536924340449d8a4787d19d366b76f
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spelling	oai:doaj.org-article:15536924340449d8a4787d19d366b76f2021-11-18T08:07:23ZZinc transporter 8 (ZnT8) expression is reduced by ischemic insults: a potential therapeutic target to prevent ischemic retinopathy.1932-620310.1371/journal.pone.0050360https://doaj.org/article/15536924340449d8a4787d19d366b76f2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23209723/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The zinc (Zn(++)) transporter ZnT8 plays a crucial role in zinc homeostasis. It's been reported that an acute decrease in ZnT8 levels impairs β cell function and Zn(++) homeostasis, which contribute to the pathophysiology of diabetes mellitus (DM). Although ZnT8 expression has been detected in the retinal pigment epithelium (RPE), its expression profile in the retina has yet to be determined. Furthermore, the link between diabetes and ischemic retinopathy is well documented; nevertheless, the molecular mechanism(s) of such link has yet to be defined. Our aims were to; investigate the expression profile of ZnT8 in the retina; address the influence of ischemia on such expression; and evaluate the influence of YC-1; (3-(50-hydroxymethyl-20-furyl)-1-benzyl indazole), a hypoxia inducible factor-1 (HIF-1) inhibitor, on the status of ZnT8 expression. We used real-time RT-PCR, immunohistochemistry, and Western blot in the mouse model of oxygen-induced retinopathy (OIR) and Müller cells to evaluate the effects of ischemia/hypoxia and YC-1 on ZnT8 expression. Our data indicate that ZnT8 was strongly expressed in the outer nuclear layer (ONL), outer plexiform layer (OPL), ganglion cell layer (GCL), and nerve fiber layer (NFL), whereas the photoreceptor layer (PRL), inner nuclear layer (INL) and inner plexiform layer (IPL) showed moderate ZnT8 immunoreactivity. Furthermore, we demonstrate that retinal ischemic insult induces a significant downregulation of ZnT8 at the message and protein levels, YC-1 rescues the injured retina by restoring the ZnT8 to its basal homeostatic levels in the neovascular retinas. Our data indicate that ischemic retinopathy maybe mediated by aberrant Zn(++) homeostasis caused by ZnT8 downregulation, whereas YC-1 plays a neuroprotective role against ischemic insult. Therefore, targeting ZnT8 provides a therapeutic strategy to combat neovascular eye diseases.Michael DeniroFutwan A Al-MohannaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 11, p e50360 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Michael Deniro Futwan A Al-Mohanna Zinc transporter 8 (ZnT8) expression is reduced by ischemic insults: a potential therapeutic target to prevent ischemic retinopathy.
description	The zinc (Zn(++)) transporter ZnT8 plays a crucial role in zinc homeostasis. It's been reported that an acute decrease in ZnT8 levels impairs β cell function and Zn(++) homeostasis, which contribute to the pathophysiology of diabetes mellitus (DM). Although ZnT8 expression has been detected in the retinal pigment epithelium (RPE), its expression profile in the retina has yet to be determined. Furthermore, the link between diabetes and ischemic retinopathy is well documented; nevertheless, the molecular mechanism(s) of such link has yet to be defined. Our aims were to; investigate the expression profile of ZnT8 in the retina; address the influence of ischemia on such expression; and evaluate the influence of YC-1; (3-(50-hydroxymethyl-20-furyl)-1-benzyl indazole), a hypoxia inducible factor-1 (HIF-1) inhibitor, on the status of ZnT8 expression. We used real-time RT-PCR, immunohistochemistry, and Western blot in the mouse model of oxygen-induced retinopathy (OIR) and Müller cells to evaluate the effects of ischemia/hypoxia and YC-1 on ZnT8 expression. Our data indicate that ZnT8 was strongly expressed in the outer nuclear layer (ONL), outer plexiform layer (OPL), ganglion cell layer (GCL), and nerve fiber layer (NFL), whereas the photoreceptor layer (PRL), inner nuclear layer (INL) and inner plexiform layer (IPL) showed moderate ZnT8 immunoreactivity. Furthermore, we demonstrate that retinal ischemic insult induces a significant downregulation of ZnT8 at the message and protein levels, YC-1 rescues the injured retina by restoring the ZnT8 to its basal homeostatic levels in the neovascular retinas. Our data indicate that ischemic retinopathy maybe mediated by aberrant Zn(++) homeostasis caused by ZnT8 downregulation, whereas YC-1 plays a neuroprotective role against ischemic insult. Therefore, targeting ZnT8 provides a therapeutic strategy to combat neovascular eye diseases.
format	article
author	Michael Deniro Futwan A Al-Mohanna
author_facet	Michael Deniro Futwan A Al-Mohanna
author_sort	Michael Deniro
title	Zinc transporter 8 (ZnT8) expression is reduced by ischemic insults: a potential therapeutic target to prevent ischemic retinopathy.
title_short	Zinc transporter 8 (ZnT8) expression is reduced by ischemic insults: a potential therapeutic target to prevent ischemic retinopathy.
title_full	Zinc transporter 8 (ZnT8) expression is reduced by ischemic insults: a potential therapeutic target to prevent ischemic retinopathy.
title_fullStr	Zinc transporter 8 (ZnT8) expression is reduced by ischemic insults: a potential therapeutic target to prevent ischemic retinopathy.
title_full_unstemmed	Zinc transporter 8 (ZnT8) expression is reduced by ischemic insults: a potential therapeutic target to prevent ischemic retinopathy.
title_sort	zinc transporter 8 (znt8) expression is reduced by ischemic insults: a potential therapeutic target to prevent ischemic retinopathy.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/15536924340449d8a4787d19d366b76f
work_keys_str_mv	AT michaeldeniro zinctransporter8znt8expressionisreducedbyischemicinsultsapotentialtherapeutictargettopreventischemicretinopathy AT futwanaalmohanna zinctransporter8znt8expressionisreducedbyischemicinsultsapotentialtherapeutictargettopreventischemicretinopathy
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Zinc transporter 8 (ZnT8) expression is reduced by ischemic insults: a potential therapeutic target to prevent ischemic retinopathy.

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