Endurance training reverts heart mitochondrial dysfunction, permeability transition and apoptotic signaling in long-term severe hyperglycemia
- PMID: 20654738
- DOI: 10.1016/j.mito.2010.07.005
Endurance training reverts heart mitochondrial dysfunction, permeability transition and apoptotic signaling in long-term severe hyperglycemia
Abstract
The present study analyzed the effects of endurance training against cardiac mitochondrial dysfunction, particularly on the susceptibility to mitochondrial permeability transition pore (MPTP) induction in streptozotocin (STZ)-induced hyperglycemia. Twenty-four young male Wistar rats were randomly assigned into sedentary citrate (SED+CIT), sedentary type I diabetes (SED+STZ; 50mg/kg), T+CIT (14-week treadmill running, 60min/day) and T+STZ (injected 4weeks before training). After 18weeks, isolated heart mitochondria were used for in vitro oxygen consumption and transmembrane potential (∆Ψ) assessment. Cyclosporin-A (CyclA)-sensitive osmotic swelling and Ca(2+) fluxes were measured to study MPTP susceptibility. Voltage-dependent anion channel (VDAC), adenine nucleotide translocator (ANT), cyclophilin D (CypD), transcription factor A (Tfam), Bax, Bcl-2 contents, caspase-3 and -9 activities were determined. In the sedentary group, long-term severe hyperglycemia decreased state 3, CCCP-induced uncoupling and increased oligomycin-inhibited respiration, state 4 and lag phase with glutamate-malate. A decreased state 3 and state 4 with succinate were observed. Moreover, hyperglycemia decreased Ca(2+) uptake and increased CyclA-sensitive Ca(2+) release and Ca(2+)-induced mitochondrial swelling. The oxygen consumption and ∆Ψ parameters impaired by long-term severe hyperglycemia were reverted by endurance training (SED+STZ vs. T+STZ). Training increased mitochondrial Ca(2+) uptake and decreased Ca(2+) release in hyperglycemic groups. Additionally, endurance training reverted the hyperglycemia-induced CypD elevation, attenuating decrease of ANT, VDAC and Tfam. Moreover, training prevented the STZ-induced elevation in Bax, Bax-to-Bcl-2 ratio, caspase-3 and -9 and the increased Bcl-2. Endurance training reestablished heart mitochondrial respiratory dysfunction caused by long-term severe hyperglycemia and reduced the increased susceptibility to MPTP induction probably by modulation of MPTP regulatory proteins.
Copyright © 2010 Elsevier B.V. and Mitochondria Research Society. All rights reserved.
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