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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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | Metabolites |
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| Online Access: | https://www.mdpi.com/2218-1989/13/2/278 |
| _version_ | 1797619296728252416 |
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| author | Leonidas Mavroudakis Ingela Lanekoff |
| author_facet | Leonidas Mavroudakis Ingela Lanekoff |
| author_sort | Leonidas Mavroudakis |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-11T08:26:07Z |
| format | Article |
| id | doaj.art-4aab8a88117f4baca21252a10f86fdea |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-11T08:26:07Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-4aab8a88117f4baca21252a10f86fdea2023-11-16T22:05:22ZengMDPI AGMetabolites2218-19892023-02-0113227810.3390/metabo13020278Ischemic Stroke Causes Disruptions in the Carnitine Shuttle SystemLeonidas Mavroudakis0Ingela Lanekoff1Department of Chemistry—BMC, Uppsala University, 75237 Uppsala, SwedenDepartment of Chemistry—BMC, Uppsala University, 75237 Uppsala, SwedenGaining 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.https://www.mdpi.com/2218-1989/13/2/278acylcarnitinesmass spectrometry imagingischemic strokenano-DESI |
| spellingShingle | Leonidas Mavroudakis Ingela Lanekoff Ischemic Stroke Causes Disruptions in the Carnitine Shuttle System Metabolites acylcarnitines mass spectrometry imaging ischemic stroke nano-DESI |
| 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 | acylcarnitines mass spectrometry imaging ischemic stroke nano-DESI |
| url | https://www.mdpi.com/2218-1989/13/2/278 |
| work_keys_str_mv | AT leonidasmavroudakis ischemicstrokecausesdisruptionsinthecarnitineshuttlesystem AT ingelalanekoff ischemicstrokecausesdisruptionsinthecarnitineshuttlesystem |