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Ischemic Stroke Causes Disruptions in the Carnitine Shuttle System

Gaining a deep understanding of the molecular mechanisms underlying ischemic stroke is necessary to develop treatment alternatives. Ischemic stroke is known to cause a cellular energy imbalance when glucose supply is deprived, enhancing the role for energy production via β-oxidation where acylcarnit...

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Autores principales: Mavroudakis, Leonidas, Lanekoff, Ingela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9968086/
https://www.ncbi.nlm.nih.gov/pubmed/36837897
http://dx.doi.org/10.3390/metabo13020278
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author Mavroudakis, Leonidas
Lanekoff, Ingela
author_facet Mavroudakis, Leonidas
Lanekoff, Ingela
author_sort Mavroudakis, Leonidas
collection PubMed
description Gaining a deep understanding of the molecular mechanisms underlying ischemic stroke is necessary to develop treatment alternatives. Ischemic stroke is known to cause a cellular energy imbalance when glucose supply is deprived, enhancing the role for energy production via β-oxidation where acylcarnitines are essential for the transportation of fatty acids into the mitochondria. Although traditional bulk analysis methods enable sensitive detection of acylcarnitines, they do not provide information on their abundances in various tissue regions. However, with quantitative mass spectrometry imaging the detected concentrations and spatial distributions of endogenous molecules can be readily obtained in an unbiased way. Here, we use pneumatically assisted nanospray desorption electrospray ionization mass spectrometry imaging (PA nano-DESI MSI) doped with internal standards to study the distributions of acylcarnitines in mouse brain affected by stroke. The internal standards enable quantitative imaging and annotation of endogenous acylcarnitines is achieved by studying fragmentation patterns. We report a significant accumulation of long-chain acylcarnitines due to ischemia in brain tissue of the middle cerebral artery occlusion (MCAO) stroke model. Further, we estimate activities of carnitine transporting enzymes and demonstrate disruptions in the carnitine shuttle system that affects the β-oxidation in the mitochondria. Our results show the importance for quantitative monitoring of metabolite distributions in distinct tissue regions to understand cell compensation mechanisms involved in handling damage caused by stroke.
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spelling pubmed-99680862023-02-27 Ischemic Stroke Causes Disruptions in the Carnitine Shuttle System Mavroudakis, Leonidas Lanekoff, Ingela Metabolites Article Gaining a deep understanding of the molecular mechanisms underlying ischemic stroke is necessary to develop treatment alternatives. Ischemic stroke is known to cause a cellular energy imbalance when glucose supply is deprived, enhancing the role for energy production via β-oxidation where acylcarnitines are essential for the transportation of fatty acids into the mitochondria. Although traditional bulk analysis methods enable sensitive detection of acylcarnitines, they do not provide information on their abundances in various tissue regions. However, with quantitative mass spectrometry imaging the detected concentrations and spatial distributions of endogenous molecules can be readily obtained in an unbiased way. Here, we use pneumatically assisted nanospray desorption electrospray ionization mass spectrometry imaging (PA nano-DESI MSI) doped with internal standards to study the distributions of acylcarnitines in mouse brain affected by stroke. The internal standards enable quantitative imaging and annotation of endogenous acylcarnitines is achieved by studying fragmentation patterns. We report a significant accumulation of long-chain acylcarnitines due to ischemia in brain tissue of the middle cerebral artery occlusion (MCAO) stroke model. Further, we estimate activities of carnitine transporting enzymes and demonstrate disruptions in the carnitine shuttle system that affects the β-oxidation in the mitochondria. Our results show the importance for quantitative monitoring of metabolite distributions in distinct tissue regions to understand cell compensation mechanisms involved in handling damage caused by stroke. MDPI 2023-02-14 /pmc/articles/PMC9968086/ /pubmed/36837897 http://dx.doi.org/10.3390/metabo13020278 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mavroudakis, Leonidas
Lanekoff, Ingela
Ischemic Stroke Causes Disruptions in the Carnitine Shuttle System
title Ischemic Stroke Causes Disruptions in the Carnitine Shuttle System
title_full Ischemic Stroke Causes Disruptions in the Carnitine Shuttle System
title_fullStr Ischemic Stroke Causes Disruptions in the Carnitine Shuttle System
title_full_unstemmed Ischemic Stroke Causes Disruptions in the Carnitine Shuttle System
title_short Ischemic Stroke Causes Disruptions in the Carnitine Shuttle System
title_sort ischemic stroke causes disruptions in the carnitine shuttle system
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9968086/
https://www.ncbi.nlm.nih.gov/pubmed/36837897
http://dx.doi.org/10.3390/metabo13020278
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