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Enhancement of Cellular Antioxidant-Defence Preserves Diastolic Dysfunction via Regulation of Both Diastolic Zn(2+) and Ca(2+) and Prevention of RyR2-Leak in Hyperglycemic Cardiomyocytes

We examined whether cellular antioxidant-defence enhancement preserves diastolic dysfunction via regulation of both diastolic intracellular free Zn(2+) and Ca(2+) levels ([Zn(2+)](i) and [Ca(2+)](i)) levels N-acetyl cysteine (NAC) treatment (4 weeks) of diabetic rats preserved altered cellular redox...

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Autores principales: Tuncay, Erkan, Okatan, Esma N., Toy, Aysegul, Turan, Belma
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3945998/
https://www.ncbi.nlm.nih.gov/pubmed/24693334
http://dx.doi.org/10.1155/2014/290381
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author Tuncay, Erkan
Okatan, Esma N.
Toy, Aysegul
Turan, Belma
author_facet Tuncay, Erkan
Okatan, Esma N.
Toy, Aysegul
Turan, Belma
author_sort Tuncay, Erkan
collection PubMed
description We examined whether cellular antioxidant-defence enhancement preserves diastolic dysfunction via regulation of both diastolic intracellular free Zn(2+) and Ca(2+) levels ([Zn(2+)](i) and [Ca(2+)](i)) levels N-acetyl cysteine (NAC) treatment (4 weeks) of diabetic rats preserved altered cellular redox state and also prevented diabetes-induced tissue damage and diastolic dysfunction with marked normalizations in the resting [Zn(2+)](i) and [Ca(2+)](i). The kinetic parameters of transient changes in Zn(2+) and Ca(2+) under electrical stimulation and the spatiotemporal properties of Zn(2+) and Ca(2+) sparks in resting cells are found to be normal in the treated diabetic group. Biochemical analysis demonstrated that the NAC treatment also antagonized hyperphosphorylation of cardiac ryanodine receptors (RyR2) and significantly restored depleted protein levels of both RyR2 and calstabin2. Incubation of cardiomyocytes with 10 µM ZnCl(2) exerted hyperphosphorylation in RyR2 as well as higher phosphorphorylations in both PKA and CaMKII in a concentration-dependent manner, similar to hyperglycemia. Our present data also showed that a subcellular oxidative stress marker, NF-κB, can be activated if the cells are exposed directly to Zn(2+). We thus for the first time report that an enhancement of antioxidant defence in diabetics via directly targeting heart seems to prevent diastolic dysfunction due to modulation of RyR2 macromolecular-complex thereby leading to normalized [Ca(2+)](i) and [Zn(2+)](i) in cardiomyocytes.
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spelling pubmed-39459982014-04-01 Enhancement of Cellular Antioxidant-Defence Preserves Diastolic Dysfunction via Regulation of Both Diastolic Zn(2+) and Ca(2+) and Prevention of RyR2-Leak in Hyperglycemic Cardiomyocytes Tuncay, Erkan Okatan, Esma N. Toy, Aysegul Turan, Belma Oxid Med Cell Longev Research Article We examined whether cellular antioxidant-defence enhancement preserves diastolic dysfunction via regulation of both diastolic intracellular free Zn(2+) and Ca(2+) levels ([Zn(2+)](i) and [Ca(2+)](i)) levels N-acetyl cysteine (NAC) treatment (4 weeks) of diabetic rats preserved altered cellular redox state and also prevented diabetes-induced tissue damage and diastolic dysfunction with marked normalizations in the resting [Zn(2+)](i) and [Ca(2+)](i). The kinetic parameters of transient changes in Zn(2+) and Ca(2+) under electrical stimulation and the spatiotemporal properties of Zn(2+) and Ca(2+) sparks in resting cells are found to be normal in the treated diabetic group. Biochemical analysis demonstrated that the NAC treatment also antagonized hyperphosphorylation of cardiac ryanodine receptors (RyR2) and significantly restored depleted protein levels of both RyR2 and calstabin2. Incubation of cardiomyocytes with 10 µM ZnCl(2) exerted hyperphosphorylation in RyR2 as well as higher phosphorphorylations in both PKA and CaMKII in a concentration-dependent manner, similar to hyperglycemia. Our present data also showed that a subcellular oxidative stress marker, NF-κB, can be activated if the cells are exposed directly to Zn(2+). We thus for the first time report that an enhancement of antioxidant defence in diabetics via directly targeting heart seems to prevent diastolic dysfunction due to modulation of RyR2 macromolecular-complex thereby leading to normalized [Ca(2+)](i) and [Zn(2+)](i) in cardiomyocytes. Hindawi Publishing Corporation 2014 2014-02-13 /pmc/articles/PMC3945998/ /pubmed/24693334 http://dx.doi.org/10.1155/2014/290381 Text en Copyright © 2014 Erkan Tuncay et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Tuncay, Erkan
Okatan, Esma N.
Toy, Aysegul
Turan, Belma
Enhancement of Cellular Antioxidant-Defence Preserves Diastolic Dysfunction via Regulation of Both Diastolic Zn(2+) and Ca(2+) and Prevention of RyR2-Leak in Hyperglycemic Cardiomyocytes
title Enhancement of Cellular Antioxidant-Defence Preserves Diastolic Dysfunction via Regulation of Both Diastolic Zn(2+) and Ca(2+) and Prevention of RyR2-Leak in Hyperglycemic Cardiomyocytes
title_full Enhancement of Cellular Antioxidant-Defence Preserves Diastolic Dysfunction via Regulation of Both Diastolic Zn(2+) and Ca(2+) and Prevention of RyR2-Leak in Hyperglycemic Cardiomyocytes
title_fullStr Enhancement of Cellular Antioxidant-Defence Preserves Diastolic Dysfunction via Regulation of Both Diastolic Zn(2+) and Ca(2+) and Prevention of RyR2-Leak in Hyperglycemic Cardiomyocytes
title_full_unstemmed Enhancement of Cellular Antioxidant-Defence Preserves Diastolic Dysfunction via Regulation of Both Diastolic Zn(2+) and Ca(2+) and Prevention of RyR2-Leak in Hyperglycemic Cardiomyocytes
title_short Enhancement of Cellular Antioxidant-Defence Preserves Diastolic Dysfunction via Regulation of Both Diastolic Zn(2+) and Ca(2+) and Prevention of RyR2-Leak in Hyperglycemic Cardiomyocytes
title_sort enhancement of cellular antioxidant-defence preserves diastolic dysfunction via regulation of both diastolic zn(2+) and ca(2+) and prevention of ryr2-leak in hyperglycemic cardiomyocytes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3945998/
https://www.ncbi.nlm.nih.gov/pubmed/24693334
http://dx.doi.org/10.1155/2014/290381
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