Enhancing Glycolysis Protects against Ischemia-Reperfusion Injury by Reducing ROS Production
Beltran, Claudia (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Pardo, Rosario (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Bou-Teen, Diana (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Ruiz Meana, Marisol (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Villena, Josep A. (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Ferreira-Gonzalez, Ignacio (Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública)
Barba, Ignasi (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Universitat Autònoma de Barcelona

Date:	2020
Abstract:	After myocardial ischemia-reperfusion, fatty acid oxidation shows fast recovery while glucose oxidation rates remain depressed. A metabolic shift aimed at increasing glucose oxidation has shown to be beneficial in models of myocardial ischemia-reperfusion. However, strategies aimed at increasing glucose consumption in the clinic have provided mixed results and have not yet reached routine clinical practice. A better understanding of the mechanisms underlying the protection afforded by increased glucose oxidation may facilitate the transfer to the clinic. The purpose of this study was to evaluate if the modulation of reactive oxygen species (ROS) was involved in the protection afforded by increased glucose oxidation. Firstly, we characterized an H9C2 cellular model in which the use of glucose or galactose as substrates can modulate glycolysis and oxidative phosphorylation pathways. In this model, there were no differences in morphology, cell number, or ATP and PCr levels. However, galactose-grown cells consumed more oxygen and had an increased Krebs cycle turnover, while cells grown in glucose had increased aerobic glycolysis rate as demonstrated by higher lactate and alanine production. Increased aerobic glycolysis was associated with reduced ROS levels and protected the cells against simulated ischemia-reperfusion injury. Furthermore, ROS scavenger N-acetyl cysteine (NAC) was able to reduce the amount of ROS and to prevent cell death. Lastly, cells grown in galactose showed higher activation of mTOR/Akt signaling pathways. In conclusion, our results provide evidence indicating that metabolic shift towards increased glycolysis reduces mitochondrial ROS production and prevents cell death during ischemia-reperfusion injury.
Grants:	Ministerio de Economía, Industria y Competitividad PI14/01431 Ministerio de Economía, Industria y Competitividad PI17/01397 Agència de Gestió d'Ajuts Universitaris i de Recerca SGR-1807 Ministerio de Economía, Industria y Competitividad BPU2015-64462-R
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Metabolic shift ; Heart ; Myocardial infarction
Published in:	Metabolites, Vol. 10 (march 2020) , ISSN 2218-1989

DOI: 10.3390/metabo10040132
PMID: 32235559

16 p, 2.5 MB

The record appears in these collections:
Articles > Research articles
Articles > Published articles