Stimulation of glycolysis promotes cardiomyocyte proliferation after injury in adult zebrafish.

Autor: Fukuda R; Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.; The German Centre for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany., Marín-Juez R; Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.; The German Centre for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany., El-Sammak H; Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.; The German Centre for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany., Beisaw A; Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.; The German Centre for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany., Ramadass R; Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.; The German Centre for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany., Kuenne C; The Cardio-Pulmonary Institute (CPI) and Deep Sequencing Platform, Bad Nauheim, Germany., Guenther S; The Cardio-Pulmonary Institute (CPI) and Deep Sequencing Platform, Bad Nauheim, Germany.; Bioinformatics and Deep Sequencing Platform, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany., Konzer A; The German Centre for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.; Biomolecular Mass Spectrometry, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany., Bhagwat AM; The German Centre for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.; Biomolecular Mass Spectrometry, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany., Graumann J; The German Centre for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.; Biomolecular Mass Spectrometry, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany., Stainier DY; Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.; The German Centre for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
Jazyk: angličtina
Zdroj: EMBO reports [EMBO Rep] 2020 Aug 05; Vol. 21 (8), pp. e49752. Date of Electronic Publication: 2020 Jul 09.
DOI: 10.15252/embr.201949752
Abstrakt: Cardiac metabolism plays a crucial role in producing sufficient energy to sustain cardiac function. However, the role of metabolism in different aspects of cardiomyocyte regeneration remains unclear. Working with the adult zebrafish heart regeneration model, we first find an increase in the levels of mRNAs encoding enzymes regulating glucose and pyruvate metabolism, including pyruvate kinase M1/2 (Pkm) and pyruvate dehydrogenase kinases (Pdks), especially in tissues bordering the damaged area. We further find that impaired glycolysis decreases the number of proliferating cardiomyocytes following injury. These observations are supported by analyses using loss-of-function models for the metabolic regulators Pkma2 and peroxisome proliferator-activated receptor gamma coactivator 1 alpha. Cardiomyocyte-specific loss- and gain-of-function manipulations of pyruvate metabolism using Pdk3 as well as a catalytic subunit of the pyruvate dehydrogenase complex (PDC) reveal its importance in cardiomyocyte dedifferentiation and proliferation after injury. Furthermore, we find that PDK activity can modulate cell cycle progression and protrusive activity in mammalian cardiomyocytes in culture. Our findings reveal new roles for cardiac metabolism and the PDK-PDC axis in cardiomyocyte behavior following cardiac injury.
(© 2020 The Authors. Published under the terms of the CC BY NC ND 4.0 license.)
Databáze: MEDLINE
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