Abstract 13274: Upregulation of Catalase by Activation of PPARγ is Cardioprotective Against Oxidative Stress in Newborn Heart
Peroxisome proliferator-activated receptor-γ (PPARγ) regulates the antioxidant enzyme catalase (CAT) in vascular cell lines which protects against ischemia/reperfusion injury. Early surgical repair for congenital heart defects can cause oxidative stress in newborn hearts, which have been shown to be sensitive to ischemia/reperfusion. It is unknown if activation of PPARγ is cardioprotective against oxidative stress in newborn heart. We measured the expression of PPARγ and CAT in newborn rabbit and adult heart. Both PPARγ and CAT mRNA and protein levels were lower in newborn (P<0.05, n=8). Newborn and adult isolated cardiomyocytes were exposed to oxidative stress by application of hydrogen peroxide (H2O2). H2O2 significantly decreased sarcomere shortening in newborn cells (37.7±3.1%, p<0.05) but not adult and with no change in the intracellular calcium transients, confirming increased sensitivity of newborn to oxidative stress. Hearts were then pretreated with an activator of PPARγ (rosiglitazone, ROSI) and exposed to H2O2. ROSI upregulated CAT mRNA by 64.4±5.1% (P<0.05, n=8) in newborn heart and by 18.8±2.0% in adult heart. CAT activity was increased by 38.0±4.4% (P<0.05, n=6) in newborn heart with ROSI with no change in adult. Furthermore, ROSI attenuated mitochondrial outer membrane damage in newborn but not adult heart. ROSI also inhibited release of lactate dehydrogenase (LDH) in H2O2 stressed newborn with no effect in adult heart. To determine the role of CAT in ROSI protection of the newborn, we used amino-triazole (CAT inhibitor, AT, 50μM) with or without ROSI during H2O2 stress. We found that the LDH release increased more in the AT+ROSI group compared to the AT group in newborn heart, with no difference in adult heart (P<0.05, n=4–6). In conclusion, activation of PPARγ is cardioprotective against oxidative stress in newborn heart but not in adult heart by up-regulation and activation of catalase.
- © 2010 by American Heart Association, Inc.