Mitochondrial H 2 O 2 metabolism as central event of heart complex I syndrome in early diabetes.

Autor: Rukavina-Mikusic IA; Universidad de Buenos Aires (UBA), Facultad de Farmacia y Bioquímica, Departamento de Ciencias Químicas, Cátedra de Fisicoquímica, Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Instituto de Bioquímica y Medicina Molecular, Prof. Dr. Alberto Boveris (IBIMOL, UBA-CONICET), Fisicoquímica, Buenos Aires, Argentina., Rey M; Universidad de Buenos Aires (UBA), Facultad de Farmacia y Bioquímica, Departamento de Ciencias Químicas, Cátedra de Fisicoquímica, Buenos Aires, Argentina., Adán Areán JS; Universidad de Buenos Aires (UBA), Facultad de Farmacia y Bioquímica, Departamento de Ciencias Químicas, Cátedra de Fisicoquímica, Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Instituto de Bioquímica y Medicina Molecular, Prof. Dr. Alberto Boveris (IBIMOL, UBA-CONICET), Fisicoquímica, Buenos Aires, Argentina., Vanasco V; Universidad de Buenos Aires (UBA), Facultad de Farmacia y Bioquímica, Departamento de Ciencias Químicas, Cátedra de Fisicoquímica, Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Instituto de Bioquímica y Medicina Molecular, Prof. Dr. Alberto Boveris (IBIMOL, UBA-CONICET), Fisicoquímica, Buenos Aires, Argentina., Alvarez S; Universidad de Buenos Aires (UBA), Facultad de Farmacia y Bioquímica, Departamento de Ciencias Químicas, Cátedra de Fisicoquímica, Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Instituto de Bioquímica y Medicina Molecular, Prof. Dr. Alberto Boveris (IBIMOL, UBA-CONICET), Fisicoquímica, Buenos Aires, Argentina., Valdez LB; Universidad de Buenos Aires (UBA), Facultad de Farmacia y Bioquímica, Departamento de Ciencias Químicas, Cátedra de Fisicoquímica, Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Instituto de Bioquímica y Medicina Molecular, Prof. Dr. Alberto Boveris (IBIMOL, UBA-CONICET), Fisicoquímica, Buenos Aires, Argentina. Electronic address: lbvaldez@ffyb.uba.ar.
Jazyk: angličtina
Zdroj: Free radical biology & medicine [Free Radic Biol Med] 2023 May 20; Vol. 201, pp. 66-75. Date of Electronic Publication: 2023 Mar 15.
DOI: 10.1016/j.freeradbiomed.2023.03.011
Abstrakt: Hydrogen peroxide is the main metabolite effective in redox regulation and it is considered an insulinomimetic agent, with insulin signalling being essential for normal mitochondrial function in cardiomyocytes. Therefore, the aim of this work was to deeply analyse the heart mitochondrial H 2 O 2 metabolism, in the early stage of type 1 diabetes. Diabetes was induced by Streptozotocin (STZ, single dose, 60 mg × kg -1 , ip.) in male Wistar rats and the animals were sacrificed 10 days after injection. Mitochondrial membrane potential and ATP production, using malate-glutamate as substrates, in the heart of diabetic animals were like the ones observed in control group. Mn-SOD activity was lower (15%) in the heart of diabetic rats even though its expression was increased (29%). The increment in heart mitochondrial H 2 O 2 production (117%) in diabetic animals was accompanied by an enhancement in the activities and expressions of glutathione peroxidase (26% and 42%) and of catalase (200% and 133%), with no changes in the peroxiredoxin activity, leading to [H 2 O 2 ] ss ∼40 nM. Heart mitochondrial lipid peroxidation and protein nitration were higher in STZ-injected animals (45% and 42%) than in control group. The mitochondrial membrane potential and ATP production preservation suggest the absence of irreversible damage at this early stage of diabetes 1. The increase in mitochondrial [H 2 O 2 ] ss above the physiological range, but still below supraphysiological concentration (∼100 nM) seems to be part of the adaptive response triggered in cardiomyocytes due to the absence of insulin. The signs of mitochondrial dysfunction observed in this very early stage of diabetes are consistent with the mitochondrial entity called ″complex I syndrome″.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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