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Revista argentina de cardiología
On-line version ISSN 1850-3748
Abstract
RUKAVINA-MIKUSIC, IVANA A.; REY, MICAELA; TRIPODI, VALERIA and VALDEZ, LAURA B.. Mitochondrial Complex I, H2O2 and NO as Prodromal Signals of Cardiac Dysfunction in Type 1 Diabetes. Rev. argent. cardiol. [online]. 2021, vol.89, n.2, pp.92-97. Epub Apr 01, 2021. ISSN 1850-3748. http://dx.doi.org/10.7775/rac.es.v89.i2.19865.
Background:
Previous results from our laboratory suggest that heart mitochondrial dysfunction precedes myocardial failure associated with sustained hyperglycemia.
Purpose:
The aim of this study was to analyze the early events that take place in heart mitochondria in a type 1 diabetes mellitus (DM) model.
Methods:
Male Wistar rats were injected with streptozotocin (STZ; 60 mg/kg, ip.) to induce DM. They were euthanized 10 or 14 days later and the heart mitochondrial fraction was obtained.
Results:
State 3 O2 consumption in the presence of malate-glutamate (21%) or succinate (16%), and complex I-III (27%), II-III (24%) and IV (22%) activities were lower in diabetic animals 14 days after STZ injection. When animals were euthanized at day 10, only state 3 O2 consumption sustained by complex I substrates (23%) and its corresponding respiratory control (30%) were lower in rats injected with STZ, in agreement with reduced complex I-III activity (17%). These changes were accompanied by increased H2O2 (117%), NO (30%) and ONOO- (~225%) production rates, mtNOS expression (29%) and O2 - (~150%) and NO (~30%) steady-state concentrations, together with a decrease in Mn-SOD activity (15%) and mitochondrial [GSSG+GSH] (28%), without changes in PGC-1α expression.
Conclusion:
Complex I dysfunction and increased H2O2, NO and ONOO- production rates can be considered subcellular prodromal signals of the mitochondrial damage that precedes myocardial dysfunction in diabetes.
Keywords : Type 1 Diabetes Mellitus; Hyperglycemia; Mitochondrial Complex I; Heart mitochondria; Nitric Oxide; Hydrogen Peroxide.