title: Specific antioxidant selenoproteins are induced in the heart during hypertrophy.
abstract: Selenium (Se) is thought to confer cardioprotective effects through the actions of antioxidant selenoprotein enzymes that directly limit levels of ROS such as hydrogen peroxide (H(2)O(2)) or that reverse oxidative damage to lipids and proteins. To determine how the selenoproteome responds to myocardial hypertrophy, two mouse models were employed: triidothyronine (T3)- or isoproterenol (ISO)-treatment. After 7days of T3- and ISO-treatment, cardiac stress was demonstrated by increased H(2)O(2) and caspase-3 activity. Neither treatment produced significant increases in phospholipid peroxidation or TUNEL-positive cells, suggesting that antioxidant systems were protecting the cardiomyocytes from damage. Many selenoprotein mRNAs were induced by T3- and ISO-treatment, with levels of methionine sulfoxide reductase 1 (MsrB1, also called SelR) mRNA showing the largest increases. MsrB enzymatic activity was also elevated in both models of cardiac stress, while glutathione peroxidase (GPx) activity and thioredoxin reductase (Trxrd) activity were moderately and nonsignificantly increased, respectively. Western blot assays revealed a marked increase in MsrB1 and moderate increases in GPx3, GPx4, and Trxrd1, particularly in T3-treated hearts. Thus, the main response of the selenoproteome during hypertrophy does not involve increased GPx1, but increased GPx3 for reducing extracellular H(2)O(2) and increased GPx4, Trxrd1, and MsrB1 for minimizing intracellular oxidative damage.
authors.affiliation: Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI 96813, USA.
authors.forename: FuKun W
authors.initials: FW
authors.lastname: Hoffmann
authors.forename: Ann S
authors.initials: AS
authors.lastname: Hashimoto
authors.forename: Byung Cheon
authors.initials: BC
authors.lastname: Lee
authors.forename: Aaron H
authors.initials: AH
authors.lastname: Rose
authors.forename: Ralph V
authors.initials: RV
authors.lastname: Shohet
authors.forename: Peter R
authors.initials: PR
authors.lastname: Hoffmann
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D006984:Hypertrophy / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology*; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000235:genetics; D051140:Selenoproteins / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D000975:Antioxidants; D012333:RNA, Messenger; D051140:Selenoproteins