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Branched Chain Amino Acids Promote ATP Production Via Translocation of Glucose Transporters
PURPOSE: We have previously shown that maintenance of ATP levels is a promising strategy for preventing neuronal cell death, and that branched chain amino acids (BCAAs) enhanced cellular ATP levels in cultured cells and antagonized cell death. BCAAs attenuated photoreceptor degeneration and retinal...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Association for Research in Vision and Ophthalmology
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9363681/ https://www.ncbi.nlm.nih.gov/pubmed/35930269 http://dx.doi.org/10.1167/iovs.63.9.7 |
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author | Iwai, Sachiko Hasegawa, Tomoko Ikeda, Hanako Ohashi Tsujikawa, Akitaka |
author_facet | Iwai, Sachiko Hasegawa, Tomoko Ikeda, Hanako Ohashi Tsujikawa, Akitaka |
author_sort | Iwai, Sachiko |
collection | PubMed |
description | PURPOSE: We have previously shown that maintenance of ATP levels is a promising strategy for preventing neuronal cell death, and that branched chain amino acids (BCAAs) enhanced cellular ATP levels in cultured cells and antagonized cell death. BCAAs attenuated photoreceptor degeneration and retinal ganglion cell death in rodent models of retinal degeneration or glaucoma. This study aimed to elucidate the mechanisms through which BCAAs enhance ATP production. METHODS: Intracellular ATP concentration was measured in HeLa cells under glycolysis and citric acid cycle inhibited conditions. Next, glucose uptake was quantified in HeLa cells and in 661W retinal photoreceptor-derived cells under glycolysis inhibition, endoplasmic reticulum stress, and glucose transporters (GLUTs) inhibited conditions, by measuring the fluorescence of fluorescently labeled deoxy-glucose analog using flow cytometry. Then, the intracellular behavior of GLUT1 and GLUT3 were observed in HeLa or 661W cells transfected with enhanced green fluorescent protein-GLUTs. RESULTS: BCAAs recovered intracellular ATP levels during glycolysis inhibition and during citric acid cycle inhibition. BCAAs significantly increased glucose uptake and recovered decreased glucose uptake induced by endoplasmic reticulum stress or glycolysis inhibition. However, BCAAs were unable to increase intracellular ATP levels or glucose uptake when GLUTs were inhibited. Fluorescence microscopy revealed that supplementation of BCAAs enhanced the translocation of GLUTs proteins to the plasma membrane over time. CONCLUSIONS: BCAAs increase ATP production by promoting glucose uptake through promotion of glucose transporters translocation to the plasma membrane. These results may help expand the clinical application of BCAAs in retinal neurodegenerative diseases, such as glaucoma and retinal degeneration. |
format | Online Article Text |
id | pubmed-9363681 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | The Association for Research in Vision and Ophthalmology |
record_format | MEDLINE/PubMed |
spelling | pubmed-93636812022-08-11 Branched Chain Amino Acids Promote ATP Production Via Translocation of Glucose Transporters Iwai, Sachiko Hasegawa, Tomoko Ikeda, Hanako Ohashi Tsujikawa, Akitaka Invest Ophthalmol Vis Sci Retina PURPOSE: We have previously shown that maintenance of ATP levels is a promising strategy for preventing neuronal cell death, and that branched chain amino acids (BCAAs) enhanced cellular ATP levels in cultured cells and antagonized cell death. BCAAs attenuated photoreceptor degeneration and retinal ganglion cell death in rodent models of retinal degeneration or glaucoma. This study aimed to elucidate the mechanisms through which BCAAs enhance ATP production. METHODS: Intracellular ATP concentration was measured in HeLa cells under glycolysis and citric acid cycle inhibited conditions. Next, glucose uptake was quantified in HeLa cells and in 661W retinal photoreceptor-derived cells under glycolysis inhibition, endoplasmic reticulum stress, and glucose transporters (GLUTs) inhibited conditions, by measuring the fluorescence of fluorescently labeled deoxy-glucose analog using flow cytometry. Then, the intracellular behavior of GLUT1 and GLUT3 were observed in HeLa or 661W cells transfected with enhanced green fluorescent protein-GLUTs. RESULTS: BCAAs recovered intracellular ATP levels during glycolysis inhibition and during citric acid cycle inhibition. BCAAs significantly increased glucose uptake and recovered decreased glucose uptake induced by endoplasmic reticulum stress or glycolysis inhibition. However, BCAAs were unable to increase intracellular ATP levels or glucose uptake when GLUTs were inhibited. Fluorescence microscopy revealed that supplementation of BCAAs enhanced the translocation of GLUTs proteins to the plasma membrane over time. CONCLUSIONS: BCAAs increase ATP production by promoting glucose uptake through promotion of glucose transporters translocation to the plasma membrane. These results may help expand the clinical application of BCAAs in retinal neurodegenerative diseases, such as glaucoma and retinal degeneration. The Association for Research in Vision and Ophthalmology 2022-08-05 /pmc/articles/PMC9363681/ /pubmed/35930269 http://dx.doi.org/10.1167/iovs.63.9.7 Text en Copyright 2022 The Authors https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License. |
spellingShingle | Retina Iwai, Sachiko Hasegawa, Tomoko Ikeda, Hanako Ohashi Tsujikawa, Akitaka Branched Chain Amino Acids Promote ATP Production Via Translocation of Glucose Transporters |
title | Branched Chain Amino Acids Promote ATP Production Via Translocation of Glucose Transporters |
title_full | Branched Chain Amino Acids Promote ATP Production Via Translocation of Glucose Transporters |
title_fullStr | Branched Chain Amino Acids Promote ATP Production Via Translocation of Glucose Transporters |
title_full_unstemmed | Branched Chain Amino Acids Promote ATP Production Via Translocation of Glucose Transporters |
title_short | Branched Chain Amino Acids Promote ATP Production Via Translocation of Glucose Transporters |
title_sort | branched chain amino acids promote atp production via translocation of glucose transporters |
topic | Retina |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9363681/ https://www.ncbi.nlm.nih.gov/pubmed/35930269 http://dx.doi.org/10.1167/iovs.63.9.7 |
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