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C-Peptide Reduces Mitochondrial Superoxide Generation by Restoring Complex I Activity in High Glucose-Exposed Renal Microvascular Endothelial Cells

Hyperglycemia-mediated microvascular damage has been proposed to originate from excessive generation of mitochondrial superoxide in endothelial cells and is the suggested mechanism by which the pathogenesis of diabetes-induced renal damage occurs. C-peptide has been shown to ameliorate diabetes-indu...

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Autores principales: Vejandla, Himani, Hollander, John M., Kothur, Anand, Brock, Robert W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International Scholarly Research Network 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3388427/
https://www.ncbi.nlm.nih.gov/pubmed/22778984
http://dx.doi.org/10.5402/2012/162802
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author Vejandla, Himani
Hollander, John M.
Kothur, Anand
Brock, Robert W.
author_facet Vejandla, Himani
Hollander, John M.
Kothur, Anand
Brock, Robert W.
author_sort Vejandla, Himani
collection PubMed
description Hyperglycemia-mediated microvascular damage has been proposed to originate from excessive generation of mitochondrial superoxide in endothelial cells and is the suggested mechanism by which the pathogenesis of diabetes-induced renal damage occurs. C-peptide has been shown to ameliorate diabetes-induced renal impairment. Yet, the mechanisms underlying this protective benefit remain unclear. The objective of this study was to determine whether C-peptide affords protection to renal microvascular endothelial cell mitochondria during hyperglycemia. Conditionally immortalized murine renal microvascular endothelial cells (MECs) were exposed to low (5.5 mM) or high glucose (25 mM) media with either C-peptide (6.6 nM) or its scrambled sequence control peptide for 24 or 48 hours. Respiratory control ratio, a measure of mitochondrial electrochemical coupling, was significantly higher in high glucose renal MECs treated with C-peptide than those of high glucose alone. C-peptide also restored high glucose-induced renal MEC mitochondrial membrane potential changes back to their basal low glucose state. Moreover, C-peptide prevented the excessive mitochondrial superoxide generation and concomitant reductions in mitochondrial complex I activity which are mediated by the exposure of the renal MECs to high glucose. Together, these data demonstrate that C-peptide protects against high glucose-induced generation of mitochondrial superoxide in renal MECs via restoration of basal mitochondrial function.
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spelling pubmed-33884272012-07-09 C-Peptide Reduces Mitochondrial Superoxide Generation by Restoring Complex I Activity in High Glucose-Exposed Renal Microvascular Endothelial Cells Vejandla, Himani Hollander, John M. Kothur, Anand Brock, Robert W. ISRN Endocrinol Research Article Hyperglycemia-mediated microvascular damage has been proposed to originate from excessive generation of mitochondrial superoxide in endothelial cells and is the suggested mechanism by which the pathogenesis of diabetes-induced renal damage occurs. C-peptide has been shown to ameliorate diabetes-induced renal impairment. Yet, the mechanisms underlying this protective benefit remain unclear. The objective of this study was to determine whether C-peptide affords protection to renal microvascular endothelial cell mitochondria during hyperglycemia. Conditionally immortalized murine renal microvascular endothelial cells (MECs) were exposed to low (5.5 mM) or high glucose (25 mM) media with either C-peptide (6.6 nM) or its scrambled sequence control peptide for 24 or 48 hours. Respiratory control ratio, a measure of mitochondrial electrochemical coupling, was significantly higher in high glucose renal MECs treated with C-peptide than those of high glucose alone. C-peptide also restored high glucose-induced renal MEC mitochondrial membrane potential changes back to their basal low glucose state. Moreover, C-peptide prevented the excessive mitochondrial superoxide generation and concomitant reductions in mitochondrial complex I activity which are mediated by the exposure of the renal MECs to high glucose. Together, these data demonstrate that C-peptide protects against high glucose-induced generation of mitochondrial superoxide in renal MECs via restoration of basal mitochondrial function. International Scholarly Research Network 2012-06-21 /pmc/articles/PMC3388427/ /pubmed/22778984 http://dx.doi.org/10.5402/2012/162802 Text en Copyright © 2012 Himani Vejandla 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
Vejandla, Himani
Hollander, John M.
Kothur, Anand
Brock, Robert W.
C-Peptide Reduces Mitochondrial Superoxide Generation by Restoring Complex I Activity in High Glucose-Exposed Renal Microvascular Endothelial Cells
title C-Peptide Reduces Mitochondrial Superoxide Generation by Restoring Complex I Activity in High Glucose-Exposed Renal Microvascular Endothelial Cells
title_full C-Peptide Reduces Mitochondrial Superoxide Generation by Restoring Complex I Activity in High Glucose-Exposed Renal Microvascular Endothelial Cells
title_fullStr C-Peptide Reduces Mitochondrial Superoxide Generation by Restoring Complex I Activity in High Glucose-Exposed Renal Microvascular Endothelial Cells
title_full_unstemmed C-Peptide Reduces Mitochondrial Superoxide Generation by Restoring Complex I Activity in High Glucose-Exposed Renal Microvascular Endothelial Cells
title_short C-Peptide Reduces Mitochondrial Superoxide Generation by Restoring Complex I Activity in High Glucose-Exposed Renal Microvascular Endothelial Cells
title_sort c-peptide reduces mitochondrial superoxide generation by restoring complex i activity in high glucose-exposed renal microvascular endothelial cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3388427/
https://www.ncbi.nlm.nih.gov/pubmed/22778984
http://dx.doi.org/10.5402/2012/162802
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