Isoform-specific downregulation of peroxiredoxin in human failing myocardium.
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.
Brixius
Klara
K
Department of Molecular and Cellular Sport Medicine, Institute of Cardiology and Sport Medicine, German Sport University, Germany.
Schwinger
Robert H G
RH
Hoyer
Felix
F
Napp
Andreas
A
Renner
Robert
R
Bölck
Birgit
B
Kümin
Angelika
A
Fischer
Uwe
U
Mehlhorn
Uwe
U
Werner
Sabine
S
Bloch
Wilhelm
W
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
D015415:Biomarkers; D007527:Isoenzymes; D012333:RNA, Messenger; D010544:Peroxidases; D054464:Peroxiredoxins