期刊
FREE RADICAL BIOLOGY AND MEDICINE
卷 53, 期 2, 页码 208-215出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2012.05.014
关键词
PPAR gamma; Oxidative stress; Hydrogen peroxide; Catalase; Newborn heart
资金
- Children's Healthcare of Atlanta
Regulation of catalase (CAT) by peroxisome proliferator-activated receptor-gamma (PPAR gamma) was investigated to determine if PPAR gamma activation provides cardioprotection from oxidative stress caused by hydrogen peroxide (H2O2) in an age-dependent manner. Left ventricular developed pressure (LVDP) was measured in Langendorff perfused newborn or adult rabbit hearts, exposed to 200 mu M H2O2, with perfusion of rosiglitazone (RGZ) or pioglitazone (PGZ). PPAR gamma agonists. We found: (1) H2O2 significantly decreased sarcomere shortening in newborn ventricular cells but not in adult cells. Lactate dehydrogenase (LDH) release occurred earlier in newborn than in adult heart, which may be due, in part, to the lower expression of CAT in newborn heart. (2) RGZ increased CAT mRNA and protein as well as activity in newborn but not in adult heart. GW9662 (PPAR gamma blocker) eliminated the increased CAT mRNA by RGZ. (3) In newborn heart, RGZ and PGZ treatment inhibited release of LDH in response to H2O2 compared to H2O2 alone. GW9662 decreased this inhibition. (4) LVDP was significantly higher in both RGZ + H2O2 and PGZ + H2O2 groups than in the H2O2 group. Block of PPAR gamma abolished this effect. In contrast, there was no effect of RGZ in adult. (5) The cardioprotective effects of RGZ were abolished by inhibition of CAT. In conclusion, PPAR gamma activation is cardioprotective to H2O2-induced stress in the newborn heart by upregulation of catalase. These data suggest that PPAR gamma activation may be an effective therapy for the young cardiac patient. (C) 2012 Elsevier Inc. All rights reserved.
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