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Antioxidative enzymes in human hearts with idiopathic dilated cardiomyopathy
1Klinik III für Innere Medizin der Universität zu Köln, Joseph-Stelzmann-Strasse 9, Köln, D-50924, Germany. Anselm.Baeumer@medizin.uni-koeln.de
Insights
Heart failure reduces catalase activity in the heart muscle, despite normal gene and protein levels. This decrease in hydrogen peroxide scavenging may alter cellular redox balance, impacting signaling pathways.
Area of Science:
- Cardiology
- Biochemistry
- Molecular Biology
Background:
- Reactive oxygen species (ROS) play a critical role in cellular function and disease.
- Imbalances in ROS contribute to the pathophysiology of heart failure.
- Enzymatic antioxidant defense systems are crucial for mitigating ROS-induced damage.
Purpose of the Study:
- To investigate intracellular enzymatic pathways involved in ROS elimination in failing myocardium.
- To compare enzyme activities, mRNA, and protein levels of key antioxidant enzymes between healthy and heart failure patients.
- To explore potential post-transcriptional regulation of antioxidant enzymes in heart failure.
Main Methods:
- Measurement of left ventricular enzyme activities, mRNA, and protein levels.
- Quantification of catalase (CAT), glutathione peroxidase (GPX), mitochondrial superoxide dismutase (Mn-SOD), and cytosolic superoxide dismutase (Cu/Zn-SOD).
- Assessment of lipid peroxidation products (malondialdehyde, 4-hydroxy-alkenals) and nitrotyrosine as indirect free radical markers.
Main Results:
- A significant decrease in CAT activity was observed in failing myocardium compared to controls (P<0.01).
- mRNA and protein levels for CAT remained unchanged, suggesting post-transcriptional regulation.
- Activities, mRNA, and protein levels of GPX, Mn-SOD, and Cu/Zn-SOD were similar between groups.
- No significant differences in lipid peroxidation products or nitrotyrosine were detected.
Conclusions:
- Decreased myocardial catalase activity in heart failure appears to be regulated post-transcriptionally.
- Reduced capacity to scavenge hydrogen peroxide may shift the intracellular redox balance.
- This shift could potentially activate redox-sensitive signaling pathways in failing hearts.
Abstract:
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.