title: Aerobic interval training attenuates mitochondrial dysfunction in rats post-myocardial infarction: roles of mitochondrial network dynamics.
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.
authors.affiliation: Department of Pharmacology, College of Medicine, Xi'an Jiaotong University, Xi'an 710061, China. jianghk88@126.com.
authors.forename: Hong-Ke
authors.initials: HK
authors.lastname: Jiang
authors.affiliation: Department of Pharmacology, College of Medicine, Xi'an Jiaotong University, Xi'an 710061, China. wangyh26@126.com.
authors.forename: You-Hua
authors.initials: YH
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, College of Medicine, Xi'an Jiaotong University, Xi'an 710061, China. xjtusunlei@126.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Pharmacology, College of Medicine, Xi'an Jiaotong University, Xi'an 710061, China. hexi1818@163.com.
authors.forename: Xi
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Pharmacology, College of Medicine, Xi'an Jiaotong University, Xi'an 710061, China. zmxjtu@126.com.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Center for Mitochondrial Biology and Medicine, Key Laboratory of Biomedical Information Engineering of the Ministry of Education, School of Life Science and Technology, Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China. zhfeng@sibs.ac.cn.
authors.forename: Zhi-Hui
authors.initials: ZH
authors.lastname: Feng
authors.affiliation: Department of Pharmacology, College of Medicine, Xi'an Jiaotong University, Xi'an 710061, China. yxs@mail.xjtu.edu.cn.
authors.forename: Xiao-Jiang
authors.initials: XJ
authors.lastname: Yu
authors.affiliation: Department of Pharmacology, College of Medicine, Xi'an Jiaotong University, Xi'an 710061, China. zwj@mail.xjtu.edu.cn.
authors.forename: Wei-Jin
authors.initials: WJ
authors.lastname: Zang
mesh_terms: D000244:Adenosine Diphosphate / Q000032:analysis; D000818:Animals; D034281:Dynamins / Q000096:biosynthesis; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000096:biosynthesis; D006321:Heart / Q000502:physiology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis; D008929:Mitochondria, Heart / Q000473:pathology*; D063154:Mitochondrial Dynamics / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000096:biosynthesis; D009203:Myocardial Infarction / Q000473:pathology*; D010101:Oxygen Consumption / Q000502:physiology*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010805:Physical Conditioning, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors / Q000096:biosynthesis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; C489709:Mfn1 protein, rat; D024101:Mitochondrial Proteins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D000244:Adenosine Diphosphate; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020558:GTP Phosphohydrolases; C489710:Mfn2 protein, rat; C498811:Opa1 protein, rat; C519851:Dnm1l protein, rat; D034281:Dynamins