Endurance training reverts heart mitochondrial dysfunction, permeability transition and apoptotic signaling in long-term severe hyperglycemia

• Type: Article in International Scientific Journal
• Date: 2011

Authors

lumini-oliveira, j (Author) Other; magalhaes, j (Author) FADEUP; pereira, cv (Author) Other; moreira, ac (Author) Other; oliveira, pj (Author) Other; ascensao, a (Author) FADEUP

Journal

Title: Mitochondrion

Vol. 11

Pages: 54-63

ISSN: 1567-7249

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 42 Citations

Scopus - 40 Citations

Scientific classification

FOS: Natural sciences > Biological sciences

Other information

Authenticus ID: P-002-Z5H

DOI: 10.1016/j.mito.2010.07.005

Abstract (EN): 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 + CID, sedentary type I diabetes (SED + STZ: 50 mg/kg), T + CIT (14-week treadmill running, 60 min/day) and T + STZ (injected 4 weeks before training). After 18 weeks, isolated heart mitochondria were used for in vitro oxygen consumption and transmembrane potential (Delta Psi) 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 Delta Psi 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10