Microarrays, Enzymatic Assays, and MALDI-MS for Determining Specific Alterations to Mitochondrial Electron Transport Chain Activity, ROS Formation, and Lipid Composition in a Monkey Model of Parkinson’s Disease
Multiple evidences suggest that mitochondrial dysfunction is implicated in the pathogenesis of Parkinson’s disease via the selective cell death of dopaminergic neurons, such as that which occurs after prolonged exposure to the mitochondrial electron transport chain (ETC) complex I inhibitor, 1-methy...
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MDPI AG
2023-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/6/5470 |
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| author | María Dolores García-Fernández Ane Larrea Roberto Fernández Rafael Rodríguez-Puertas Egoitz Astigarraga Iván Manuel Gabriel Barreda-Gómez |
| author_facet | María Dolores García-Fernández Ane Larrea Roberto Fernández Rafael Rodríguez-Puertas Egoitz Astigarraga Iván Manuel Gabriel Barreda-Gómez |
| author_sort | María Dolores García-Fernández |
| collection | DOAJ |
| description | Multiple evidences suggest that mitochondrial dysfunction is implicated in the pathogenesis of Parkinson’s disease via the selective cell death of dopaminergic neurons, such as that which occurs after prolonged exposure to the mitochondrial electron transport chain (ETC) complex I inhibitor, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrine (MPTP). However, the effects of chronic MPTP on the ETC complexes and on enzymes of lipid metabolism have not yet been thoroughly determined. To face these questions, the enzymatic activities of ETC complexes and the lipidomic profile of MPTP-treated non-human primate samples were determined using cell membrane microarrays from different brain areas and tissues. MPTP treatment induced an increase in complex II activity in the olfactory bulb, putamen, caudate, and <i>substantia nigra</i>, where a decrease in complex IV activity was observed. The lipidomic profile was also altered in these areas, with a reduction in the phosphatidylserine (38:1) content being especially relevant. Thus, MPTP treatment not only modulates ETC enzymes, but also seems to alter other mitochondrial enzymes that regulate the lipid metabolism. Moreover, these results show that a combination of cell membrane microarrays, enzymatic assays, and MALDI-MS provides a powerful tool for identifying and validating new therapeutic targets that might accelerate the drug discovery process. |
| first_indexed | 2024-03-11T06:26:37Z |
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| id | doaj.art-f09a7f5e902c4f689748efb7092342af |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T06:26:37Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-f09a7f5e902c4f689748efb7092342af2023-11-17T11:34:19ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-03-01246547010.3390/ijms24065470Microarrays, Enzymatic Assays, and MALDI-MS for Determining Specific Alterations to Mitochondrial Electron Transport Chain Activity, ROS Formation, and Lipid Composition in a Monkey Model of Parkinson’s DiseaseMaría Dolores García-Fernández0Ane Larrea1Roberto Fernández2Rafael Rodríguez-Puertas3Egoitz Astigarraga4Iván Manuel5Gabriel Barreda-Gómez6Research and Development Department, IMG Pharma Biotech S.L., 48160 Derio, SpainResearch and Development Department, IMG Pharma Biotech S.L., 48160 Derio, SpainResearch and Development Department, IMG Pharma Biotech S.L., 48160 Derio, SpainDepartment of Pharmacology, Faculty of Medicine and Nursing, University of the Basque Country, UPV/EHU, 48940 Leioa, SpainResearch and Development Department, IMG Pharma Biotech S.L., 48160 Derio, SpainDepartment of Pharmacology, Faculty of Medicine and Nursing, University of the Basque Country, UPV/EHU, 48940 Leioa, SpainResearch and Development Department, IMG Pharma Biotech S.L., 48160 Derio, SpainMultiple evidences suggest that mitochondrial dysfunction is implicated in the pathogenesis of Parkinson’s disease via the selective cell death of dopaminergic neurons, such as that which occurs after prolonged exposure to the mitochondrial electron transport chain (ETC) complex I inhibitor, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrine (MPTP). However, the effects of chronic MPTP on the ETC complexes and on enzymes of lipid metabolism have not yet been thoroughly determined. To face these questions, the enzymatic activities of ETC complexes and the lipidomic profile of MPTP-treated non-human primate samples were determined using cell membrane microarrays from different brain areas and tissues. MPTP treatment induced an increase in complex II activity in the olfactory bulb, putamen, caudate, and <i>substantia nigra</i>, where a decrease in complex IV activity was observed. The lipidomic profile was also altered in these areas, with a reduction in the phosphatidylserine (38:1) content being especially relevant. Thus, MPTP treatment not only modulates ETC enzymes, but also seems to alter other mitochondrial enzymes that regulate the lipid metabolism. Moreover, these results show that a combination of cell membrane microarrays, enzymatic assays, and MALDI-MS provides a powerful tool for identifying and validating new therapeutic targets that might accelerate the drug discovery process.https://www.mdpi.com/1422-0067/24/6/5470microarraymitochondriaParkinson’s diseaseMALDI imaging mass spectrometry |
| spellingShingle | María Dolores García-Fernández Ane Larrea Roberto Fernández Rafael Rodríguez-Puertas Egoitz Astigarraga Iván Manuel Gabriel Barreda-Gómez Microarrays, Enzymatic Assays, and MALDI-MS for Determining Specific Alterations to Mitochondrial Electron Transport Chain Activity, ROS Formation, and Lipid Composition in a Monkey Model of Parkinson’s Disease International Journal of Molecular Sciences microarray mitochondria Parkinson’s disease MALDI imaging mass spectrometry |
| title | Microarrays, Enzymatic Assays, and MALDI-MS for Determining Specific Alterations to Mitochondrial Electron Transport Chain Activity, ROS Formation, and Lipid Composition in a Monkey Model of Parkinson’s Disease |
| title_full | Microarrays, Enzymatic Assays, and MALDI-MS for Determining Specific Alterations to Mitochondrial Electron Transport Chain Activity, ROS Formation, and Lipid Composition in a Monkey Model of Parkinson’s Disease |
| title_fullStr | Microarrays, Enzymatic Assays, and MALDI-MS for Determining Specific Alterations to Mitochondrial Electron Transport Chain Activity, ROS Formation, and Lipid Composition in a Monkey Model of Parkinson’s Disease |
| title_full_unstemmed | Microarrays, Enzymatic Assays, and MALDI-MS for Determining Specific Alterations to Mitochondrial Electron Transport Chain Activity, ROS Formation, and Lipid Composition in a Monkey Model of Parkinson’s Disease |
| title_short | Microarrays, Enzymatic Assays, and MALDI-MS for Determining Specific Alterations to Mitochondrial Electron Transport Chain Activity, ROS Formation, and Lipid Composition in a Monkey Model of Parkinson’s Disease |
| title_sort | microarrays enzymatic assays and maldi ms for determining specific alterations to mitochondrial electron transport chain activity ros formation and lipid composition in a monkey model of parkinson s disease |
| topic | microarray mitochondria Parkinson’s disease MALDI imaging mass spectrometry |
| url | https://www.mdpi.com/1422-0067/24/6/5470 |
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