title: Isoform-specific downregulation of peroxiredoxin in human failing myocardium.
abstract: Peroxiredoxins (Prx) are a family of antioxidant thioredoxin or glutathione dependent peroxidases. The major functions of Prx comprise modulation of signalling cascades that apply hydrogen peroxide (H(2)O(2)) and cellular protection against oxidative stress. Nothing is known about Prx isoforms in human myocardium. We investigated the protein expression of Prx isoforms 1-6 in human non-failing (NF, donor hearts, n=6, male, age: 53.3+/-2.1 years) and failing myocardium (DCM, orthotopic heart transplantation, dilated cardiomyopathy, n=15, male, 57.0+/-1.7 years). In addition, we performed immunohistochemical stainings and measured Prx 4 mRNA expression levels (RNAse protection assay). The protein expression of Prx 1-2 was similar in NF and DCM. The protein expression of Prx 3-6 and the mRNA-expression of Prx 4 were decreased in DCM. Immunohistochemical analyses provided evidence that all Prx isoforms are present in cardiomyocytes and endothelial cells. Whereas Prx 1-5 staining was more pronounced in endothelial cells, Prx6 staining was more evident in cardiomyocytes. This study provides evidence that Prx are differentially regulated in DCM. The selective downregulation of peroxiredoxin 3-6 isoforms may point towards a subcellular specific dysregulation of the antioxidative defence during the development of DCM.
authors.affiliation: Department of Molecular and Cellular Sport Medicine, Institute of Cardiology and Sport Medicine, German Sport University, Germany.
authors.forename: Klara
authors.initials: K
authors.lastname: Brixius
authors.forename: Robert H G
authors.initials: RH
authors.lastname: Schwinger
authors.forename: Felix
authors.initials: F
authors.lastname: Hoyer
authors.forename: Andreas
authors.initials: A
authors.lastname: Napp
authors.forename: Robert
authors.initials: R
authors.lastname: Renner
authors.forename: Birgit
authors.initials: B
authors.lastname: Bölck
authors.forename: Angelika
authors.initials: A
authors.lastname: Kümin
authors.forename: Uwe
authors.initials: U
authors.lastname: Fischer
authors.forename: Uwe
authors.initials: U
authors.lastname: Mehlhorn
authors.forename: Sabine
authors.initials: S
authors.lastname: Werner
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Bloch
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002311:Cardiomyopathy, Dilated / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation; D019084:Fluorescent Antibody Technique, Indirect; D015870:Gene Expression; D006333:Heart Failure / Q000378:metabolism* / Q000473:pathology; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D010544:Peroxidases / Q000235:genetics / Q000378:metabolism*; D054464:Peroxiredoxins; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D015415:Biomarkers; D007527:Isoenzymes; D012333:RNA, Messenger; D010544:Peroxidases; D054464:Peroxiredoxins