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The use of phosphorescence oxygen analyzer to measure the effects of rotenone and 1-methyl-4-phenylpyridinium on striatal cellular respiration in C57BL6 mice
BACKGROUND: We have previously reported on the use of the phosphorescence oxygen analyzer for measuring spinal cord cellular respiration. This analytical tool is used here to investigate the effects of two inhibitors of NADH:ubiquinone oxidoreductase, rotenone and 1-methyl-4-phenylpyridinium, on cel...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203712/ https://www.ncbi.nlm.nih.gov/pubmed/34159274 http://dx.doi.org/10.1016/j.heliyon.2021.e07219 |
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author | Al Shamsi, Mariam Haque, M.Emdadul Shahin, Allen Shaban, Sami Souid, Abdul-Kader |
author_facet | Al Shamsi, Mariam Haque, M.Emdadul Shahin, Allen Shaban, Sami Souid, Abdul-Kader |
author_sort | Al Shamsi, Mariam |
collection | PubMed |
description | BACKGROUND: We have previously reported on the use of the phosphorescence oxygen analyzer for measuring spinal cord cellular respiration. This analytical tool is used here to investigate the effects of two inhibitors of NADH:ubiquinone oxidoreductase, rotenone and 1-methyl-4-phenylpyridinium, on cellular respiration in striatal tissue. Both neurotoxins can induce Parkinson's disease-like symptoms, and have been used to study this disease in animals. Our hypothesis is that striatal cellular respiration is a sensitive biomarker for the adverse effects of toxins, and the phosphorescence oxygen analyzer can be used as a screening tool for this purpose. METHODS: Striatal fragments were collected from C57BL6 mice and immersed in Pd phosphor solution [phosphate-buffered saline, 3.0 μM ‘Pd(II)-meso-tetra (sulfophenyl) tetrabenzoporphyrin’ and 0.5% fat-free albumin, with and without 5.0 mM glucose]. The sample was transferred to a glass vial containing 2-mL Pd phosphor solution. The vial was sealed from air and placed in the instrument that measures dissolved oxygen as function of time. Immunoblots of the studied tissue were positive for the dopamine neuronal cell biomarker tyrosine hydroxylase. RESULTS: Striatal oxygen consumption was linear with time, exhibiting zero-order kinetics of oxygen reduction by cytochrome oxidase. Cyanide sensitive respiration was ≥90%, confirming oxygen was reduced by cytochrome oxidase. The rate of respiration increased by ~2-fold in the presence of glucose. Striatal oxygen consumption in the presence of rotenone or 1-methyl-4-phenylpyridinium was exponential, demonstrating impaired respiration. CONCLUSION: Striatal cellular mitochondrial oxygen consumption was impaired by the studied inhibitors of complex I of the respiratory chain. This effect is expected to deplete NAD+ (oxidized nicotinamide adenine dinucleotide), a principle driver of glycolysis. In vivo studies are required to determine if these toxin-induced metabolic derangements contribute to the development of sporadic Parkinson's disease. This analytic tool can be used to screen environmental toxins for their in vitro effects on the striatum. |
format | Online Article Text |
id | pubmed-8203712 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-82037122021-06-21 The use of phosphorescence oxygen analyzer to measure the effects of rotenone and 1-methyl-4-phenylpyridinium on striatal cellular respiration in C57BL6 mice Al Shamsi, Mariam Haque, M.Emdadul Shahin, Allen Shaban, Sami Souid, Abdul-Kader Heliyon Research Article BACKGROUND: We have previously reported on the use of the phosphorescence oxygen analyzer for measuring spinal cord cellular respiration. This analytical tool is used here to investigate the effects of two inhibitors of NADH:ubiquinone oxidoreductase, rotenone and 1-methyl-4-phenylpyridinium, on cellular respiration in striatal tissue. Both neurotoxins can induce Parkinson's disease-like symptoms, and have been used to study this disease in animals. Our hypothesis is that striatal cellular respiration is a sensitive biomarker for the adverse effects of toxins, and the phosphorescence oxygen analyzer can be used as a screening tool for this purpose. METHODS: Striatal fragments were collected from C57BL6 mice and immersed in Pd phosphor solution [phosphate-buffered saline, 3.0 μM ‘Pd(II)-meso-tetra (sulfophenyl) tetrabenzoporphyrin’ and 0.5% fat-free albumin, with and without 5.0 mM glucose]. The sample was transferred to a glass vial containing 2-mL Pd phosphor solution. The vial was sealed from air and placed in the instrument that measures dissolved oxygen as function of time. Immunoblots of the studied tissue were positive for the dopamine neuronal cell biomarker tyrosine hydroxylase. RESULTS: Striatal oxygen consumption was linear with time, exhibiting zero-order kinetics of oxygen reduction by cytochrome oxidase. Cyanide sensitive respiration was ≥90%, confirming oxygen was reduced by cytochrome oxidase. The rate of respiration increased by ~2-fold in the presence of glucose. Striatal oxygen consumption in the presence of rotenone or 1-methyl-4-phenylpyridinium was exponential, demonstrating impaired respiration. CONCLUSION: Striatal cellular mitochondrial oxygen consumption was impaired by the studied inhibitors of complex I of the respiratory chain. This effect is expected to deplete NAD+ (oxidized nicotinamide adenine dinucleotide), a principle driver of glycolysis. In vivo studies are required to determine if these toxin-induced metabolic derangements contribute to the development of sporadic Parkinson's disease. This analytic tool can be used to screen environmental toxins for their in vitro effects on the striatum. Elsevier 2021-06-05 /pmc/articles/PMC8203712/ /pubmed/34159274 http://dx.doi.org/10.1016/j.heliyon.2021.e07219 Text en © 2021 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Article Al Shamsi, Mariam Haque, M.Emdadul Shahin, Allen Shaban, Sami Souid, Abdul-Kader The use of phosphorescence oxygen analyzer to measure the effects of rotenone and 1-methyl-4-phenylpyridinium on striatal cellular respiration in C57BL6 mice |
title | The use of phosphorescence oxygen analyzer to measure the effects of rotenone and 1-methyl-4-phenylpyridinium on striatal cellular respiration in C57BL6 mice |
title_full | The use of phosphorescence oxygen analyzer to measure the effects of rotenone and 1-methyl-4-phenylpyridinium on striatal cellular respiration in C57BL6 mice |
title_fullStr | The use of phosphorescence oxygen analyzer to measure the effects of rotenone and 1-methyl-4-phenylpyridinium on striatal cellular respiration in C57BL6 mice |
title_full_unstemmed | The use of phosphorescence oxygen analyzer to measure the effects of rotenone and 1-methyl-4-phenylpyridinium on striatal cellular respiration in C57BL6 mice |
title_short | The use of phosphorescence oxygen analyzer to measure the effects of rotenone and 1-methyl-4-phenylpyridinium on striatal cellular respiration in C57BL6 mice |
title_sort | use of phosphorescence oxygen analyzer to measure the effects of rotenone and 1-methyl-4-phenylpyridinium on striatal cellular respiration in c57bl6 mice |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203712/ https://www.ncbi.nlm.nih.gov/pubmed/34159274 http://dx.doi.org/10.1016/j.heliyon.2021.e07219 |
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