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Pyruvate attenuates the anti-neoplastic effect of carnosine independently from oxidative phosphorylation

Here we analyzed whether the anti-neoplastic effect of carnosine, which inhibits glycolytic ATP production, can be antagonized by ATP production via oxidative phosphorylation fueled by pyruvate. Therefore, glioblastoma cells were cultivated in medium supplemented with glucose, galactose or pyruvate...

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Autores principales: Oppermann, Henry, Schnabel, Lutz, Meixensberger, Jürgen, Gaunitz, Frank
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5349879/
https://www.ncbi.nlm.nih.gov/pubmed/27811375
http://dx.doi.org/10.18632/oncotarget.13039
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author Oppermann, Henry
Schnabel, Lutz
Meixensberger, Jürgen
Gaunitz, Frank
author_facet Oppermann, Henry
Schnabel, Lutz
Meixensberger, Jürgen
Gaunitz, Frank
author_sort Oppermann, Henry
collection PubMed
description Here we analyzed whether the anti-neoplastic effect of carnosine, which inhibits glycolytic ATP production, can be antagonized by ATP production via oxidative phosphorylation fueled by pyruvate. Therefore, glioblastoma cells were cultivated in medium supplemented with glucose, galactose or pyruvate and in the presence or absence of carnosine. CPI-613 was employed to inhibit the entry of pyruvate into the tricarboxylic acid cycle and 2,4-dinitrophenol to inhibit oxidative phosphorylation. Energy metabolism and viability were assessed by cell based assays and histochemistry. ATP in cell lysates and dehydrogenase activity in living cells revealed a strong reduction of viability under the influence of carnosine when cells received glucose or galactose but not in the presence of pyruvate. CPI-613 and 2,4-dinitrophenol reduced viability of cells cultivated in pyruvate, but no effect was seen in the presence of glucose. No effect of carnosine on viability was observed in the presence of glucose and pyruvate even in the presence of 2,4-dinitrophenol or CPI-613. In conclusion, glioblastoma cells produce ATP from pyruvate via the tricarboxylic acid cycle and oxidative phosphorylation in the absence of a glycolytic substrate. In addition, pyruvate attenuates the anti-neoplastic effect of carnosine, even when ATP production via tricarboxylic acid cycle and oxidative phosphorylation is blocked. We also observed an inhibitory effect of carnosine on the tricarboxylic acid cycle and a stimulating effect of 2,4-dinitrophenol on glycolytic ATP production.
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spelling pubmed-53498792017-04-06 Pyruvate attenuates the anti-neoplastic effect of carnosine independently from oxidative phosphorylation Oppermann, Henry Schnabel, Lutz Meixensberger, Jürgen Gaunitz, Frank Oncotarget Research Paper Here we analyzed whether the anti-neoplastic effect of carnosine, which inhibits glycolytic ATP production, can be antagonized by ATP production via oxidative phosphorylation fueled by pyruvate. Therefore, glioblastoma cells were cultivated in medium supplemented with glucose, galactose or pyruvate and in the presence or absence of carnosine. CPI-613 was employed to inhibit the entry of pyruvate into the tricarboxylic acid cycle and 2,4-dinitrophenol to inhibit oxidative phosphorylation. Energy metabolism and viability were assessed by cell based assays and histochemistry. ATP in cell lysates and dehydrogenase activity in living cells revealed a strong reduction of viability under the influence of carnosine when cells received glucose or galactose but not in the presence of pyruvate. CPI-613 and 2,4-dinitrophenol reduced viability of cells cultivated in pyruvate, but no effect was seen in the presence of glucose. No effect of carnosine on viability was observed in the presence of glucose and pyruvate even in the presence of 2,4-dinitrophenol or CPI-613. In conclusion, glioblastoma cells produce ATP from pyruvate via the tricarboxylic acid cycle and oxidative phosphorylation in the absence of a glycolytic substrate. In addition, pyruvate attenuates the anti-neoplastic effect of carnosine, even when ATP production via tricarboxylic acid cycle and oxidative phosphorylation is blocked. We also observed an inhibitory effect of carnosine on the tricarboxylic acid cycle and a stimulating effect of 2,4-dinitrophenol on glycolytic ATP production. Impact Journals LLC 2016-11-03 /pmc/articles/PMC5349879/ /pubmed/27811375 http://dx.doi.org/10.18632/oncotarget.13039 Text en Copyright: © 2016 Oppermann et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Oppermann, Henry
Schnabel, Lutz
Meixensberger, Jürgen
Gaunitz, Frank
Pyruvate attenuates the anti-neoplastic effect of carnosine independently from oxidative phosphorylation
title Pyruvate attenuates the anti-neoplastic effect of carnosine independently from oxidative phosphorylation
title_full Pyruvate attenuates the anti-neoplastic effect of carnosine independently from oxidative phosphorylation
title_fullStr Pyruvate attenuates the anti-neoplastic effect of carnosine independently from oxidative phosphorylation
title_full_unstemmed Pyruvate attenuates the anti-neoplastic effect of carnosine independently from oxidative phosphorylation
title_short Pyruvate attenuates the anti-neoplastic effect of carnosine independently from oxidative phosphorylation
title_sort pyruvate attenuates the anti-neoplastic effect of carnosine independently from oxidative phosphorylation
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5349879/
https://www.ncbi.nlm.nih.gov/pubmed/27811375
http://dx.doi.org/10.18632/oncotarget.13039
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