Imperial College London
Alternate

ProfessorGuyRutter

Faculty of Medicine, Department of Medicine

Visiting Professor
 
 
 
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Contact

 

+44 (0)20 7594 3340g.rutter Website

 
 
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Location

 

ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Tuncay:2017:10.2337/db16-1099,
author = {Tuncay, E and Bitirim, VC and Durak, A and Carrat, GRJ and Taylor, KM and Rutter, GA and Turan, B},
doi = {10.2337/db16-1099},
journal = {Diabetes},
pages = {1346--1358},
title = {Hyperglycemia-Induced Changes in ZIP7 and ZnT7 Expression Cause Zn2+ Release From the Sarco(endo)plasmic Reticulum and Mediate ER Stress in the Heart},
url = {http://dx.doi.org/10.2337/db16-1099},
volume = {66},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Changes in cellular free Zn2+ concentration, including those in the sarco(endo)plasmicreticulum [S(E)R], are primarily coordinated by Zn2+-transporters whose identity and role inthe heart is not well established. Here, we hypothesized that ZIP7 and ZnT7 transport Zn2+ inopposing directions across the S(E)R membrane in cardiomyocytes and that changes in theiractivity may play an important role in the development of ER-stress during hyperglycemia.The subcellular S(E)R-localization of ZIP7 and ZnT7 was determined in cardiomyocytes andin isolated S(E)R-preparations. Markedly increased mRNA and protein levels of ZIP7 wereobserved in ventricular cardiomyocytes from diabetic rats or high glucose-treated H9c2 cellswhilst ZnT7 expression was low. Additionally, we observed increased ZIP7-phosphorylationin response to high glucose in vivo and in vitro. Using recombinant targeted FRET-basedsensors, we showed that hyperglycemia induced a marked redistribution of cellular free Zn2+,increasing cytosolic free Zn2+ and lowering free Zn2+ in the S(E)R. These changes involvealterations in ZIP7-phosphorylation and were suppressed by siRNA-mediated silencing ofCK2α. Opposing changes in the expression of ZIP7 and ZnT7 were also observed inhyperglycemia. We conclude that sub-cellular free Zn2+ re-distribution in the hyperglycemicheart, resulting from altered ZIP7 and ZnT7 activity, contributes to cardiac dysfunction indiabetes.
AU  - Tuncay,E
AU  - Bitirim,VC
AU  - Durak,A
AU  - Carrat,GRJ
AU  - Taylor,KM
AU  - Rutter,GA
AU  - Turan,B
DO  - 10.2337/db16-1099
EP  - 1358
PY  - 2017///
SN  - 0012-1797
SP  - 1346
TI  - Hyperglycemia-Induced Changes in ZIP7 and ZnT7 Expression Cause Zn2+ Release From the Sarco(endo)plasmic Reticulum and Mediate ER Stress in the Heart
T2  - Diabetes
UR  - http://dx.doi.org/10.2337/db16-1099
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000399799800028&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/48354
VL  - 66
ER  -
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