Aerobic interval training attenuates mitochondrial dysfunction in rats post-myocardial infarction: roles of mitochondrial network dynamics

Int J Mol Sci. 2014 Mar 26;15(4):5304-22. doi: 10.3390/ijms15045304.

Abstract

Aerobic interval training (AIT) can favorably affect cardiovascular diseases. However, the effects of AIT on post-myocardial infarction (MI)-associated mitochondrial dysfunctions remain unclear. In this study, we investigated the protective effects of AIT on myocardial mitochondria in post-MI rats by focusing on mitochondrial dynamics (fusion and fission). Mitochondrial respiratory functions (as measured by the respiratory control ratio (RCR) and the ratio of ADP to oxygen consumption (P/O)); complex activities; dynamic proteins (mitofusin (mfn) 1/2, type 1 optic atrophy (OPA1) and dynamin-related protein1 (DRP1)); nuclear peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α); and the oxidative signaling of extracellular signal-regulated kinase (ERK) 1/2, c-Jun NH2-terminal protein kinase (JNK) and P53 were observed. Post-MI rats exhibited mitochondrial dysfunction and adverse mitochondrial network dynamics (reduced fusion and increased fission), which was associated with activated ERK1/2-JNK-P53 signaling and decreased nuclear PGC-1α. After AIT, MI-associated mitochondrial dysfunction was improved (elevated RCR and P/O and enhanced complex I, III and IV activities); in addition, increased fusion (mfn2 and OPA1), decreased fission (DRP1), elevated nuclear PGC-1α and inactivation of the ERK1/2-JNK-P53 signaling were observed. These data demonstrate that AIT may restore the post-MI mitochondrial function by inhibiting dynamics pathological remodeling, which may be associated with inactivation of ERK1/2-JNK-P53 signaling and increase in nuclear PGC-1α expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate / analysis
  • Animals
  • Dynamins / biosynthesis
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • GTP Phosphohydrolases / biosynthesis
  • Heart / physiology
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • MAP Kinase Signaling System
  • Male
  • Membrane Proteins / biosynthesis
  • Mitochondria, Heart / pathology*
  • Mitochondrial Dynamics / physiology*
  • Mitochondrial Proteins / biosynthesis
  • Myocardial Infarction / pathology*
  • Oxygen Consumption / physiology*
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Physical Conditioning, Animal*
  • Rats
  • Rats, Sprague-Dawley
  • Transcription Factors / biosynthesis
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Membrane Proteins
  • Mfn1 protein, rat
  • Mitochondrial Proteins
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Ppargc1a protein, rat
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • Adenosine Diphosphate
  • Extracellular Signal-Regulated MAP Kinases
  • JNK Mitogen-Activated Protein Kinases
  • GTP Phosphohydrolases
  • Mfn2 protein, rat
  • Opa1 protein, rat
  • Dnm1l protein, rat
  • Dynamins