title: Cardioprotection from oxidative stress in the newborn heart by activation of PPARγ is mediated by catalase.
abstract: Regulation of catalase (CAT) by peroxisome proliferator-activated receptor-γ (PPARγ) was investigated to determine if PPARγ activation provides cardioprotection from oxidative stress caused by hydrogen peroxide (H(2)O(2)) in an age-dependent manner. Left ventricular developed pressure (LVDP) was measured in Langendorff perfused newborn or adult rabbit hearts, exposed to 200μM H(2)O(2), with perfusion of rosiglitazone (RGZ) or pioglitazone (PGZ), PPARγ agonists. We found: (1) H(2)O(2) 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 (PPARγ blocker) eliminated the increased CAT mRNA by RGZ. (3) In newborn heart, RGZ and PGZ treatment inhibited release of LDH in response to H(2)O(2) compared to H(2)O(2) alone. GW9662 decreased this inhibition. (4) LVDP was significantly higher in both RGZ+H(2)O(2) and PGZ+H(2)O(2) groups than in the H(2)O(2) group. Block of PPARγ 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, PPARγ activation is cardioprotective to H(2)O(2)-induced stress in the newborn heart by upregulation of catalase. These data suggest that PPARγ activation may be an effective therapy for the young cardiac patient.
authors.affiliation: Emory-Children's Center for Cardiovascular Biology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA 30322, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Jin
authors.forename: Brian H
authors.initials: BH
authors.lastname: Crawford
authors.forename: Hua
authors.initials: H
authors.lastname: Cheng
authors.forename: Talib B
authors.initials: TB
authors.lastname: Saafir
authors.forename: Mary B
authors.initials: MB
authors.lastname: Wagner
authors.forename: Zuyi
authors.initials: Z
authors.lastname: Yuan
authors.forename: Guoliang
authors.initials: G
authors.lastname: Ding
mesh_terms: D000367:Age Factors; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D009924:Organ Culture Techniques; D018384:Oxidative Stress; D047495:PPAR gamma / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000077205:Pioglitazone; D012333:RNA, Messenger / Q000096:biosynthesis; D011817:Rabbits; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D015854:Up-Regulation; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D002316:Cardiotonic Agents; D047495:PPAR gamma; D012333:RNA, Messenger; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D002374:Catalase; D000077205:Pioglitazone