info:eu-repo/semantics/article
Temporal evolution of cardiac mitochondrial dysfunction in a type 1 diabetes model. Mitochondrial complex I impairment, and H2O2 and NO productions as early subcellular events
Fecha
2020-11Registro en:
Rukavina Mikusic, Ivana Agustina; Reyna, Micaela; Martinefski, Manuela Romina; Tripodi, Valeria Paula; Valdez, Laura Batriz; Temporal evolution of cardiac mitochondrial dysfunction in a type 1 diabetes model. Mitochondrial complex I impairment, and H2O2 and NO productions as early subcellular events; Elsevier Science Inc; Free Radical Biology and Medicine; 162; 11-2020; 129-140
0891-5849
CONICET Digital
CONICET
Autor
Rukavina Mikusic, Ivana Agustina
Reyna, Micaela
Martinefski, Manuela Romina
Tripodi, Valeria Paula
Valdez, Laura Batriz
Resumen
The aim of this work was to study the early events that occur in heart mitochondria and to analyse the temporal evolution of cardiac mitochondrial dysfunction in a type 1 diabetes model. Male Wistar rats were injected with Streptozotocin (STZ, single dose, 60 mg × kg−1, i.p.) and hyperglycemic state was confirmed 72 h later. The animals were sacrificed 10 or 14 days after STZ-injection. Heart mitochondrial state 3 O2 consumption sustained by malate-glutamate (21%) or by succinate (16%), and complexes I-III (27%), II-III (24%) and IV (22%) activities were lower in STZ group, when animals were sacrificed at day 14, i.e. ~11 days of hyperglycemia. In contrast, after 10 days of STZ-injection (~7 days of hyperglycemia), only the state 3 O2 consumption sustained by malate-glutamate (23%) and its corresponding respiratory control (30%) were lower in diabetic rats, in accordance with complex I-III activity reduction (17%). Therefore, this time (~7 days of hyperglycemia) has been considered as an “early stage” of cardiac mitochondrial dysfunction. At this point, mitochondrial production rates of H2O2 (117%), NO (30%) and ONOO− (~225%), and mtNOS expression (29%) were higher; and mitochondrial SOD activity (15%) and [GSH + GSSG] (28%) were lower in diabetic rats. Linear correlations between the modified mitochondrial parameters and glycemias were observed. PGC-1α expression was similar between groups, suggesting that mitochondrial biogenesis was not triggered in this initial phase of mitochondrial dysfunction. Consequently, complex I, H2O2 and NO could be considered early subcellular signals of cardiac mitochondrial dysfunction, with NO and H2O2 being located upstream de novo synthesis of mitochondria.