Hyperglycemia Does Not Affect Iron Mediated Toxicity of Cultured Endothelial and Renal Tubular Epithelial Cells: Influence of L-Carnosine

Iron has been suggested to affect the clinical course of type 2 diabetes (T2DM) as accompanying increased intracellular iron accumulation may provide an alternative source for reactive oxygen species (ROS). Although carnosine has proven its therapeutic efficacy in rodent models of T2DM, little is kn...

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Main Authors: Shiqi Zhang, Emmanouil Ntasis, Sarah Kabtni, Jaap van den Born, Gerjan Navis, Stephan J. L. Bakker, Bernhard K. Krämer, Benito A. Yard, Sibylle J. Hauske
Format: Article
Language:English
Published: Wiley 2016-01-01
Series:Journal of Diabetes Research
Online Access:http://dx.doi.org/10.1155/2016/8710432
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author Shiqi Zhang
Emmanouil Ntasis
Sarah Kabtni
Jaap van den Born
Gerjan Navis
Stephan J. L. Bakker
Bernhard K. Krämer
Benito A. Yard
Sibylle J. Hauske
author_facet Shiqi Zhang
Emmanouil Ntasis
Sarah Kabtni
Jaap van den Born
Gerjan Navis
Stephan J. L. Bakker
Bernhard K. Krämer
Benito A. Yard
Sibylle J. Hauske
author_sort Shiqi Zhang
collection DOAJ
description Iron has been suggested to affect the clinical course of type 2 diabetes (T2DM) as accompanying increased intracellular iron accumulation may provide an alternative source for reactive oxygen species (ROS). Although carnosine has proven its therapeutic efficacy in rodent models of T2DM, little is known about its efficacy to protect cells from iron toxicity. We sought to assess if high glucose (HG) exposure makes cultured human umbilical vein endothelial cells (HUVECs) and renal proximal tubular epithelial cells (PTECs) more susceptible to metal induced toxicity and if this is ameliorated by L-carnosine. HUVECs and PTECs, cultured under normal glucose (5 mM, NG) or HG (30 mM), were challenged for 24 h with FeCl3. Cell viability was not impaired under HG conditions nor did HG increase susceptibility to FeCl3. HG did not change the expression of divalent metal transporter 1 (DMT1), ferroportin (IREG), and transferrin receptor protein 1 (TFRC). Irrespective of glucose concentrations L-carnosine prevented toxicity in a dose-dependent manner, only if it was present during the FeCl3 challenge. Hence our study indicates that iron induced cytotoxicity is not enhanced under HG conditions. L-Carnosine displayed a strong protective effect, most likely by chelation of iron mediated toxicity.
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spelling doaj-art-e40ae9809fbf4bf9a88831ab17b7146f2025-02-03T05:44:24ZengWileyJournal of Diabetes Research2314-67452314-67532016-01-01201610.1155/2016/87104328710432Hyperglycemia Does Not Affect Iron Mediated Toxicity of Cultured Endothelial and Renal Tubular Epithelial Cells: Influence of L-CarnosineShiqi Zhang0Emmanouil Ntasis1Sarah Kabtni2Jaap van den Born3Gerjan Navis4Stephan J. L. Bakker5Bernhard K. Krämer6Benito A. Yard7Sibylle J. Hauske8Vth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Center Mannheim, University of Heidelberg, 68167 Mannheim, GermanyVth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Center Mannheim, University of Heidelberg, 68167 Mannheim, GermanyVth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Center Mannheim, University of Heidelberg, 68167 Mannheim, GermanyDepartment of Nephrology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, NetherlandsDepartment of Nephrology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, NetherlandsDepartment of Nephrology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, NetherlandsVth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Center Mannheim, University of Heidelberg, 68167 Mannheim, GermanyVth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Center Mannheim, University of Heidelberg, 68167 Mannheim, GermanyVth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Center Mannheim, University of Heidelberg, 68167 Mannheim, GermanyIron has been suggested to affect the clinical course of type 2 diabetes (T2DM) as accompanying increased intracellular iron accumulation may provide an alternative source for reactive oxygen species (ROS). Although carnosine has proven its therapeutic efficacy in rodent models of T2DM, little is known about its efficacy to protect cells from iron toxicity. We sought to assess if high glucose (HG) exposure makes cultured human umbilical vein endothelial cells (HUVECs) and renal proximal tubular epithelial cells (PTECs) more susceptible to metal induced toxicity and if this is ameliorated by L-carnosine. HUVECs and PTECs, cultured under normal glucose (5 mM, NG) or HG (30 mM), were challenged for 24 h with FeCl3. Cell viability was not impaired under HG conditions nor did HG increase susceptibility to FeCl3. HG did not change the expression of divalent metal transporter 1 (DMT1), ferroportin (IREG), and transferrin receptor protein 1 (TFRC). Irrespective of glucose concentrations L-carnosine prevented toxicity in a dose-dependent manner, only if it was present during the FeCl3 challenge. Hence our study indicates that iron induced cytotoxicity is not enhanced under HG conditions. L-Carnosine displayed a strong protective effect, most likely by chelation of iron mediated toxicity.http://dx.doi.org/10.1155/2016/8710432
spellingShingle Shiqi Zhang
Emmanouil Ntasis
Sarah Kabtni
Jaap van den Born
Gerjan Navis
Stephan J. L. Bakker
Bernhard K. Krämer
Benito A. Yard
Sibylle J. Hauske
Hyperglycemia Does Not Affect Iron Mediated Toxicity of Cultured Endothelial and Renal Tubular Epithelial Cells: Influence of L-Carnosine
Journal of Diabetes Research
title Hyperglycemia Does Not Affect Iron Mediated Toxicity of Cultured Endothelial and Renal Tubular Epithelial Cells: Influence of L-Carnosine
title_full Hyperglycemia Does Not Affect Iron Mediated Toxicity of Cultured Endothelial and Renal Tubular Epithelial Cells: Influence of L-Carnosine
title_fullStr Hyperglycemia Does Not Affect Iron Mediated Toxicity of Cultured Endothelial and Renal Tubular Epithelial Cells: Influence of L-Carnosine
title_full_unstemmed Hyperglycemia Does Not Affect Iron Mediated Toxicity of Cultured Endothelial and Renal Tubular Epithelial Cells: Influence of L-Carnosine
title_short Hyperglycemia Does Not Affect Iron Mediated Toxicity of Cultured Endothelial and Renal Tubular Epithelial Cells: Influence of L-Carnosine
title_sort hyperglycemia does not affect iron mediated toxicity of cultured endothelial and renal tubular epithelial cells influence of l carnosine
url http://dx.doi.org/10.1155/2016/8710432
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