title: Alterations of mitochondrial enzymes contribute to cardiac hypertrophy before hypertension development in spontaneously hypertensive rats.
abstract: Mitochondrial dysfunction is recently thought to be tightly associated with the development of cardiac hypertrophy as well as hypertension. However, the detailed molecular events in mitochondria at early stages of hypertrophic pathogenesis are still unclear. Applying two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) combined with MALDI-TOF/TOF tandem mass spectrometry, here we identified the changed mitochondrial proteins of left ventricular mitochondria in prehypertensive/hypertensive stages of cardiac hypertrophy through comparing spontaneously hypertensive rats (SHR) and the age-matched normotensive Wistar Kyoto (WKY) rats. The results revealed that in the hypertrophic left ventricle of SHR as early as 4 weeks old with normal blood pressure, 33 mitochondrial protein spots presented significant alterations, with 17 down-regulated and 16 up-regulated. Such alterations were much greater than those in 20-week-old SHR with elevated blood pressure. Of the total alterations, the expression of two mitochondrial enzymes, trifunctional enzyme alpha subunit (Hadha) and NADH dehydrogenase 1 alpha subcomplex 10 (Ndufa10), were found to have special expression modification patterns in SHR strain. These data would provide new clues to investigate the potential contribution of mitochondrial dysfunction to the development of cardiac hypertrophy.
authors.affiliation: The Department of Geriatrics, Ren-Ji Hospital, Shanghai Jiao-Tong University School of Medicine (SJTU-SM), Shanghai 200001, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Meng
authors.forename: Xian
authors.initials: X
authors.lastname: Jin
authors.forename: Li
authors.initials: L
authors.lastname: Xia
authors.forename: Shao-Ming
authors.initials: SM
authors.lastname: Shen
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Cai
authors.forename: Guo-Qiang
authors.initials: GQ
authors.lastname: Chen
authors.forename: Li-Shun
authors.initials: LS
authors.lastname: Wang
authors.forename: Ning-Yuan
authors.initials: NY
authors.lastname: Fang
mesh_terms: D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D006332:Cardiomegaly / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D004252:DNA Mutational Analysis; D015180:Electrophoresis, Gel, Two-Dimensional; D015971:Gene Expression Regulation, Enzymologic; D006973:Hypertension / Q000201:enzymology* / Q000503:physiopathology; D008297:Male; D008929:Mitochondria, Heart / Q000201:enzymology*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D009245:NADH Dehydrogenase / Q000235:genetics / Q000378:metabolism; D017354:Point Mutation; D040901:Proteomics / Q000379:methods; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013997:Time Factors
chemical_list: D024101:Mitochondrial Proteins; D015094:3-Hydroxyacyl CoA Dehydrogenases; D009245:NADH Dehydrogenase