Nitric oxide as signaling molecule involved in early stages of cardiac mitocondrial dysfuntion in Diabetes Melitus

BOMBICINO SS; VALDEZ LB; RUKAVINA-MIKUSIC IA

Buenos Aires

Congreso; Reunion Conjunta de Sociedades de Biociencia; 2017

SAIC, SAIB, SAI, SAA, SABiologia, SABiofisica, SAFE, SAFIS, SAH, SAP

Previous results from our laboratory have shown that sustainedhyperglycemia (28 days) leads to heart mitochondrial dysfunctionwith increases in H2O2 and NO steady-state concentrations. Thismitochondrial impairment was detected in the absence of heart hypertrophyand of changes in resting cardiac performance, suggestingthat mitochondrial dysfunction precedes the onset of diabeticcardiac failure. In this scenario, H2O2 and NO could be moleculesinvolved in mitochondrion-cytosol signaling. The aim was to studythe role of NO and H2O2 in early stages of the mitochondrial dysfunction,in an experimental model of Type I Diabetes Mellitus (DM).Diabetes was induced by a single dose of Streptozoticin (60 mg/kg,ip.) in male Wistar rats. Glycemia was determined 72 hours afterinjection (C:117±6 mg/dl; DM:502±27 mg/dl). The animals were sacrificedat day 10 and heart mitochondrial fraction was isolated. State3 respiration sustained by malate-glutamate and by succinate was18% and 13% lower in diabetic than in control rats. Because of restingmitochondrial O2 consumption rates did not modify, respiratorycontrol ratios mainly declined when malate-glutamate was used assubstrate. These results agree with complexes I-III and II-III activitiesthat were lower (15 and 11%) in diabetic than in control animals.However, no difference was observed in complex IV activity. Moreover,mitochondrial GSSG/GSH ratio was higher (25%) in diabeticanimals suggesting an imbalance in cellular redox state. Preliminaryresults have shown that while mitochondrial NO production rate was18% higher in diabetic rats, H2O2 generation did not modify. Theseresults show an early mitochondrial dysfunction, after 7 days of sustainedhyperglycemia, accompanied by an increase in NO generationsuggesting that this molecule could be involved in the triggering of heart mitochondrial biogenesis in an initial phase of DM.