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Substrate Modulation of Fatty Acid Effects on Energization and Respiration of Kidney Proximal Tubules during Hypoxia/Reoxygenation

Kidney proximal tubules subjected to hypoxia/reoxygenation develop a nonesterified fatty acid-induced energetic deficit characterized by persistent partial mitochondrial deenergization that can be prevented and reversed by citric acid cycle substrates. To further assess the role of competition betwe...

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Autores principales: Bienholz, Anja, Al-Taweel, Ahmad, Roeser, Nancy F., Kribben, Andreas, Feldkamp, Thorsten, Weinberg, Joel M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3984175/
https://www.ncbi.nlm.nih.gov/pubmed/24728405
http://dx.doi.org/10.1371/journal.pone.0094584
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author Bienholz, Anja
Al-Taweel, Ahmad
Roeser, Nancy F.
Kribben, Andreas
Feldkamp, Thorsten
Weinberg, Joel M.
author_facet Bienholz, Anja
Al-Taweel, Ahmad
Roeser, Nancy F.
Kribben, Andreas
Feldkamp, Thorsten
Weinberg, Joel M.
author_sort Bienholz, Anja
collection PubMed
description Kidney proximal tubules subjected to hypoxia/reoxygenation develop a nonesterified fatty acid-induced energetic deficit characterized by persistent partial mitochondrial deenergization that can be prevented and reversed by citric acid cycle substrates. To further assess the role of competition between fatty acids and substrates on inner membrane substrate carriers in the deenergization and the contribution to deenergization of fatty acid effects on respiratory function, digitonin-permeabilized rabbit and mouse tubules were studied using either addition of exogenous oleate after control normoxic incubation or increases of endogenous fatty acids produced by hypoxia/reoxygenation. The results demonstrated major effects of matrix oxaloacetate accumulation on succinate-supported energization and respiration and their modification by fatty acids. Improvements of energization in the presence of fatty acids by glutamate were shown to result predominantly from lowering matrix oxaloacetate rather than from amelioration of transmembrane cycling of fatty acids and uncoupling. Mouse tubules had 2.5 fold higher rates of succinate utilization, which resulted in stronger effects of oxaloacetate accumulation than rabbit tubules. Hypoxia/reoxygenation induced respiratory inhibition that was more severe for complex I-dependent substrates. Fatty acids themselves did not acutely contribute to this respiratory inhibition, but lowering them during 60 min. reoxygenation to allow recovery of ATP during that period alleviated it. These data clarify the basis for the nonesterified fatty acid-induced mitochondrial energetic deficit in kidney proximal tubules that impairs structural and functional recovery and provide insight into interactions that need to be considered in the design of substrate-based interventions to improve mitochondrial function.
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spelling pubmed-39841752014-04-15 Substrate Modulation of Fatty Acid Effects on Energization and Respiration of Kidney Proximal Tubules during Hypoxia/Reoxygenation Bienholz, Anja Al-Taweel, Ahmad Roeser, Nancy F. Kribben, Andreas Feldkamp, Thorsten Weinberg, Joel M. PLoS One Research Article Kidney proximal tubules subjected to hypoxia/reoxygenation develop a nonesterified fatty acid-induced energetic deficit characterized by persistent partial mitochondrial deenergization that can be prevented and reversed by citric acid cycle substrates. To further assess the role of competition between fatty acids and substrates on inner membrane substrate carriers in the deenergization and the contribution to deenergization of fatty acid effects on respiratory function, digitonin-permeabilized rabbit and mouse tubules were studied using either addition of exogenous oleate after control normoxic incubation or increases of endogenous fatty acids produced by hypoxia/reoxygenation. The results demonstrated major effects of matrix oxaloacetate accumulation on succinate-supported energization and respiration and their modification by fatty acids. Improvements of energization in the presence of fatty acids by glutamate were shown to result predominantly from lowering matrix oxaloacetate rather than from amelioration of transmembrane cycling of fatty acids and uncoupling. Mouse tubules had 2.5 fold higher rates of succinate utilization, which resulted in stronger effects of oxaloacetate accumulation than rabbit tubules. Hypoxia/reoxygenation induced respiratory inhibition that was more severe for complex I-dependent substrates. Fatty acids themselves did not acutely contribute to this respiratory inhibition, but lowering them during 60 min. reoxygenation to allow recovery of ATP during that period alleviated it. These data clarify the basis for the nonesterified fatty acid-induced mitochondrial energetic deficit in kidney proximal tubules that impairs structural and functional recovery and provide insight into interactions that need to be considered in the design of substrate-based interventions to improve mitochondrial function. Public Library of Science 2014-04-11 /pmc/articles/PMC3984175/ /pubmed/24728405 http://dx.doi.org/10.1371/journal.pone.0094584 Text en © 2014 Bienholz et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Bienholz, Anja
Al-Taweel, Ahmad
Roeser, Nancy F.
Kribben, Andreas
Feldkamp, Thorsten
Weinberg, Joel M.
Substrate Modulation of Fatty Acid Effects on Energization and Respiration of Kidney Proximal Tubules during Hypoxia/Reoxygenation
title Substrate Modulation of Fatty Acid Effects on Energization and Respiration of Kidney Proximal Tubules during Hypoxia/Reoxygenation
title_full Substrate Modulation of Fatty Acid Effects on Energization and Respiration of Kidney Proximal Tubules during Hypoxia/Reoxygenation
title_fullStr Substrate Modulation of Fatty Acid Effects on Energization and Respiration of Kidney Proximal Tubules during Hypoxia/Reoxygenation
title_full_unstemmed Substrate Modulation of Fatty Acid Effects on Energization and Respiration of Kidney Proximal Tubules during Hypoxia/Reoxygenation
title_short Substrate Modulation of Fatty Acid Effects on Energization and Respiration of Kidney Proximal Tubules during Hypoxia/Reoxygenation
title_sort substrate modulation of fatty acid effects on energization and respiration of kidney proximal tubules during hypoxia/reoxygenation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3984175/
https://www.ncbi.nlm.nih.gov/pubmed/24728405
http://dx.doi.org/10.1371/journal.pone.0094584
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