title: The role of redox signaling in cardiac hypertrophy induced by experimental hyperthyroidism.
abstract: This study was conducted to test whether oxidative stress activates the intracellular protein kinase B (AKT1) signaling pathway, which culminates with cardiac hypertrophy in experimental hyperthyroidism. Male Wistar rats were divided into four groups: control, vitamin E, thyroxine (T(4)), and T(4)+vitamin E. Hyperthyroidism was induced by T(4) administration (12 mg/l in drinking water for 28 days). Vitamin E treatment was given during the same period via s.c. injections (20 mg/kg per day). Morphometric and hemodynamic parameters were evaluated at the end of the 4-week treatment period. Protein oxidation, redox state (reduced glutathione, GSH/glutathione dissulfide, GSSG), vitamin C, total radical-trapping antioxidant potential (TRAP), hydrogen peroxide (H2O2), and nitric oxide metabolites (NO(X)) were measured in heart homogenates. The p-AKT1/AKT1 ratio, p-glycogen-synthase kinase (GSK)3B/GSK3B ratio, FOS, and JUN myocardial protein expression were also quantified by western blot after 4 weeks. Increases in biochemical parameters, such as protein oxidation (41%), H2O2 (62%), and NO(X) (218%), and increase in the left ventricular end-diastolic pressure were observed in the T(4) group. T(4) treatment also caused a decrease in GSH/GSSG ratio (83%), vitamin C (34%), and TRAP (55%). These alterations were attenuated by vitamin E administration to the hyperthyroid rats. Expression of p-AKT1/AKT1, p-GSK3B/GSK3B, FOS, and JUN were elevated in the T(4) group (by 69, 37, 130, and 33% respectively), whereas vitamin E administration promoted a significant reduction in their expression. These results indicate that oxidative stress plays an important role in cardiac hypertrophy, and suggest redox activation of AKT1 and JUN/FOS signaling pathways with H2O2 acting as a possible intracellular mediator in this adaptive response to experimental hyperthyroidism.
authors.affiliation: Departamento de Fisiologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Sarmento Leite, 500, CEP 90050-170 Porto Alegre, RS, Brazil.
authors.forename: A S R
authors.initials: AS
authors.lastname: Araujo
authors.forename: P
authors.initials: P
authors.lastname: Schenkel
authors.forename: A T
authors.initials: AT
authors.lastname: Enzveiler
authors.forename: T R G
authors.initials: TR
authors.lastname: Fernandes
authors.forename: W A
authors.initials: WA
authors.lastname: Partata
authors.forename: S
authors.initials: S
authors.lastname: Llesuy
authors.forename: M F M
authors.initials: MF
authors.lastname: Ribeiro
authors.forename: N
authors.initials: N
authors.lastname: Khaper
authors.forename: P K
authors.initials: PK
authors.lastname: Singal
authors.forename: A
authors.initials: A
authors.lastname: Belló-Klein
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism; D015153:Blotting, Western; D006332:Cardiomegaly / Q000209:etiology* / Q000378:metabolism; D004195:Disease Models, Animal; D005978:Glutathione / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D006980:Hyperthyroidism / Q000150:complications*; D008297:Male; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D013974:Thyroxine / Q000097:blood
chemical_list: D006861:Hydrogen Peroxide; D005978:Glutathione; D001205:Ascorbic Acid; D013974:Thyroxine