title: The PPARγ agonist protects cardiomyocytes from oxidative stress and apoptosis via thioredoxin overexpression.
abstract: Oxidative stress has been implicated in the pathogenesis of various cardiovascular diseases, including ischemic heart disease and heart failure. The peroxisome proliferator-activated receptor gamma (PPARγ) agonist improves insulin sensitivity and limits tissue inflammation and cellular apoptosis, but there are few data on the relationship between the PPARγ agonist, rosiglitazone (RSG), and the thioredoxin (TRx) system in oxidatively stressed cardiomyocytes (CMCs). Here we provide evidence that the PPARγ agonist RSG protects rat CMCs from hydrogen peroxide (H2O2)-induced apoptosis by TRx overexpression. The expression levels of pAkt/Akt, pErk/Erk, survivin, Bcl-2/Bax-α, and manganese-superoxide dismutase were increased by RSG pretreatment in H2O2-injured rat CMCs. On the contrary, the expression levels of caspase-3 and p53 were decreased by RSG pretreatment. These effects of RSG were reversed by chemical inhibitors of TRx and the PPARγ antagonist. This suggests that RSG protects rCMCs from H2O2-induced oxidative stress through TRx overexpression and a PPARγ-dependent mechanism.
authors.affiliation: Department of Internal Medicine, College of Medicine, Chungbuk National UniversityCheongju, Republic of Korea.
authors.forename: Yeon-Jung
authors.initials: YJ
authors.lastname: Kim
authors.forename: Keon-Jea
authors.initials: KJ
authors.lastname: Park
authors.forename: Joong-Ki
authors.initials: JK
authors.lastname: Song
authors.forename: Tae-Jin
authors.initials: TJ
authors.lastname: Shim
authors.forename: Kazi N
authors.initials: KN
authors.lastname: Islam
authors.forename: Jang-Whan
authors.initials: JW
authors.lastname: Bae
authors.forename: Sang-Min
authors.initials: SM
authors.lastname: Kim
authors.forename: Sang-Yeub
authors.initials: SY
authors.lastname: Lee
authors.forename: Kyung-Kuk
authors.initials: KK
authors.lastname: Hwang
authors.forename: Dong-Woon
authors.initials: DW
authors.lastname: Kim
authors.forename: Myeong-Chan
authors.initials: MC
authors.lastname: Cho
authors.forename: Keun Ho
authors.initials: KH
authors.lastname: Ryu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D019610:Cytoprotection / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D047495:PPAR gamma / Q000819:agonists*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D013879:Thioredoxins / Q000235:genetics*; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D013879:Thioredoxins; D006861:Hydrogen Peroxide