Abstract
Cardiac dysfunction characterizing diabetes has been associated with mitochondrial impairments. On the other hand, endurance training (ET) provides protection against cardiac mitochondrionopathies. PURPOSE: To analyze the effects of ET on cardiac mitochondrial dysfunction caused by streptozotocin (STZ) treatment, particularly on the susceptibility to mitochondrial permeability transition pore (mPTP) opening. METHODS: Twenty four adult male Wistar rats were randomly divided into sedentary (Sed), sedentary STZ (single dose, 50 mg/kg, i.p.), ET (14 wk treadmill running, 60 min/day, 25m/min) and ET+STZ (TSTZ). After STZ injection (18 wk), isolated heart mitochondria were used for in vitro oxygen consumption and transmembrane potential (DΨ) assessment using malate-pyruvate (MP) and succinate plus rotenone (SR). Cyclosporin A(CyA)-sensitive mitochondrial osmotic swelling and Ca2+ fluxes were also measured to study mtPTP opening susceptibility. RESULTS: In sedentary groups, STZ treatment resulted in decreased state 3 (165,6±6,8 vs 136,7±5,7 natomO/min/mg; p<0,05), respiratory control ratio (9,9±0,4 vs 4,9±0,3; p<0,05), CCCP-induced uncoupled respiration (394,4±7,1 vs 277,8±6,3 natomO/min/mg; p<0,05), oligomycin-inhibited respiration (115,8±6,6 vs 74,9±7,8 natomO/min/mg; p<0,05) and increased state 4 (16,7±0,6 vs 27,3±2,5 natomO/min/mg; p<0,05), DΨ with endogenous substrates (185,9±2,9 vs 194,9±1,4mV; p<0,05) and lag phase (70,0±2,1 vs 112,0±2,1 s; p<0,05) (MP). It decreased both state 3 (394,3±7,1 vs 276,7±7,9; p<0,05) and state 4 (117,0±4,0 vs 75,4±3,9; p<0,05) with SR. STZ treatment decreased CyA-sensitive Ca2+ uptake (250,8±4,8 vs 220,8±1,4 nmol/mg; p<0,05) and release (64,8±7,0 vs 47,9±3,4; p<0,05), despite the increased swelling amplitude (3,5E6±1,9E5 vs 4,1E6±3,7E4 AU; p<0,05) in sedentary groups. The respiratory and DΨ parameters impaired by STZ treatment were reverted by ET (STZ vs TSTZ). ET increased mitochondrial Ca2+ uptake (220,8±1,4 vs 273,1±3,7; p<0,05) and decreased Ca2+ release (47,9±3,4 vs 30,1±2,1; p<0,05) in diabetic animals. CONCLUSION: ET reverted the impaired heart mitochondrial respiratory function caused by STZ and decreased the susceptibility to mtPTP opening. FCT grants SFRH/BPD/4225/2007; SFRH/BD/30906/2006.
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