Antioxidative enzymes in human hearts with idiopathic dilated cardiomyopathy.
The present study investigates intracellular enzymatic pathways involved in the elimination of reactive oxygen species in the left ventricular myocardium of 10 individuals without heart failure and 12 patients with end-stage heart failure due to idiopathic dilated cardiomyopathy. Left ventricular enzyme activities, mRNA and protein levels of the hydrogen peroxide scavenging enzymes catalase (CAT) and glutathione peroxidase (GPX), and the superoxide anion scavenging enzymes mitochondrial (Mn-SOD) and cytosolic (Cu/Zn-SOD) superoxide dismutases were measured. In failing myocardium, there was a significant decrease in CAT activity (4.83+/-0.32 U/mg v 6.59+/-0.52, P<0.01) despite unchanged mRNA expression and protein levels. GPX, Mn-SOD and Cu/Zn-SOD were similar concerning activity, mRNA and protein levels. As indirect free radical markers, similar levels of the products of lipid peroxidation, malondialdehyde and 4-hydroxy-alkenals, and similar tissue nitrotyrosin content were measured. The decrease in CAT activity appears to be a post-transcriptional mechanism. A decreased myocardial capacity to scavenge hydrogen peroxide might lead to a shift in the intracellular redox balance which potentially results in activation of redox sensitive signalling pathways. Direct reactive oxygen species mediated damage was not detected by the methods applied.
Bäumer
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AT
Klinik III für Innere Medizin der Universität zu Köln, Joseph-Stelzmann-Strasse 9, Köln, D-50924, Germany. Anselm.Baeumer@medizin.uni-koeln.de
Flesch
M
M
Wang
X
X
Shen
Q
Q
Feuerstein
G Z
GZ
Böhm
M
M
D000975:Antioxidants; D002311:Cardiomyopathy, Dilated / Q000201:enzymology* / Q000235:genetics; D002374:Catalase / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D009206:Myocardium / Q000201:enzymology*; D018384:Oxidative Stress; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*
D000975:Antioxidants; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase