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PFKM inhibits doxorubicin-induced cardiotoxicity by enhancing oxidative phosphorylation and glycolysis

Heart failure (HF) is a global pandemic which affects about 26 million people. PFKM (Phosphofructokinase, Muscle), catalyzing the phosphorylation of fructose-6-phosphate, plays a very important role in cardiovascular diseases. However, the effect of PFKM in glycolysis and HF remains to be elucidated...

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Autores principales: Zhou, Min, Sun, Xiao, Wang, Chunli, Wang, Fengdan, Fang, Chuibi, Hu, Zhenlei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9266090/
https://www.ncbi.nlm.nih.gov/pubmed/35804014
http://dx.doi.org/10.1038/s41598-022-15743-0
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author Zhou, Min
Sun, Xiao
Wang, Chunli
Wang, Fengdan
Fang, Chuibi
Hu, Zhenlei
author_facet Zhou, Min
Sun, Xiao
Wang, Chunli
Wang, Fengdan
Fang, Chuibi
Hu, Zhenlei
author_sort Zhou, Min
collection PubMed
description Heart failure (HF) is a global pandemic which affects about 26 million people. PFKM (Phosphofructokinase, Muscle), catalyzing the phosphorylation of fructose-6-phosphate, plays a very important role in cardiovascular diseases. However, the effect of PFKM in glycolysis and HF remains to be elucidated. H9c2 rat cardiomyocyte cells were treated with doxorubicin (DOX) to establish injury models, and the cell viability, apoptosis and glycolysis were measured. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) and immunoblotting were used for gene expression. DOX treatment significantly inhibited PFKM expression in H9c2 cells. Overexpression of PFKM inhibited DOX-induced cell apoptosis and DOX-decreased glycolysis and oxidative phosphorylation (OXPHOS), while silencing PFKM promoted cell apoptosis and inhibited glycolysis and OXPHOS in H9c2 cells. Moreover, PFKM regulated DOX-mediated cell viability and apoptosis through glycolysis pathway. Mechanism study showed that histone deacetylase 1 (HDAC1) inhibited H3K27ac-induced transcription of PFKM in DOX-treated cells and regulated glycolysis. PFKM could inhibit DOX-induced cardiotoxicity by enhancing OXPHOS and glycolysis, which might benefit us in developing novel therapeutics for prevention or treatment of HF.
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spelling pubmed-92660902022-07-10 PFKM inhibits doxorubicin-induced cardiotoxicity by enhancing oxidative phosphorylation and glycolysis Zhou, Min Sun, Xiao Wang, Chunli Wang, Fengdan Fang, Chuibi Hu, Zhenlei Sci Rep Article Heart failure (HF) is a global pandemic which affects about 26 million people. PFKM (Phosphofructokinase, Muscle), catalyzing the phosphorylation of fructose-6-phosphate, plays a very important role in cardiovascular diseases. However, the effect of PFKM in glycolysis and HF remains to be elucidated. H9c2 rat cardiomyocyte cells were treated with doxorubicin (DOX) to establish injury models, and the cell viability, apoptosis and glycolysis were measured. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) and immunoblotting were used for gene expression. DOX treatment significantly inhibited PFKM expression in H9c2 cells. Overexpression of PFKM inhibited DOX-induced cell apoptosis and DOX-decreased glycolysis and oxidative phosphorylation (OXPHOS), while silencing PFKM promoted cell apoptosis and inhibited glycolysis and OXPHOS in H9c2 cells. Moreover, PFKM regulated DOX-mediated cell viability and apoptosis through glycolysis pathway. Mechanism study showed that histone deacetylase 1 (HDAC1) inhibited H3K27ac-induced transcription of PFKM in DOX-treated cells and regulated glycolysis. PFKM could inhibit DOX-induced cardiotoxicity by enhancing OXPHOS and glycolysis, which might benefit us in developing novel therapeutics for prevention or treatment of HF. Nature Publishing Group UK 2022-07-08 /pmc/articles/PMC9266090/ /pubmed/35804014 http://dx.doi.org/10.1038/s41598-022-15743-0 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Zhou, Min
Sun, Xiao
Wang, Chunli
Wang, Fengdan
Fang, Chuibi
Hu, Zhenlei
PFKM inhibits doxorubicin-induced cardiotoxicity by enhancing oxidative phosphorylation and glycolysis
title PFKM inhibits doxorubicin-induced cardiotoxicity by enhancing oxidative phosphorylation and glycolysis
title_full PFKM inhibits doxorubicin-induced cardiotoxicity by enhancing oxidative phosphorylation and glycolysis
title_fullStr PFKM inhibits doxorubicin-induced cardiotoxicity by enhancing oxidative phosphorylation and glycolysis
title_full_unstemmed PFKM inhibits doxorubicin-induced cardiotoxicity by enhancing oxidative phosphorylation and glycolysis
title_short PFKM inhibits doxorubicin-induced cardiotoxicity by enhancing oxidative phosphorylation and glycolysis
title_sort pfkm inhibits doxorubicin-induced cardiotoxicity by enhancing oxidative phosphorylation and glycolysis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9266090/
https://www.ncbi.nlm.nih.gov/pubmed/35804014
http://dx.doi.org/10.1038/s41598-022-15743-0
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