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This Article Accepted manuscript (PDF) All Versions of this Article: JME-08-0024v1 41/6/423    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Araujo, A. Articles by Bello-Klein, A. Search for Related Content PubMed PubMed Citation Articles by Araujo, A. Articles by Bello-Klein, A.

A Araujo, Porto Alegre, Brazil
P Schenkel, Porto Alegre, Brazil
A Enzveiler, Porto Alegre, Brazil
T Fernandes, Porto Alegre, Brazil
W Partata, Porto Alegre, Brazil
S Llesuy, Buenos Aires, Argentina
M Ribeiro, Porto Alegre, Brazil
N Khaper, Ontario, Canada
P Singal, Winnipeg, Canada
A Bello-Klein, Physiology, UFRGS, Porto Alegre, 90050-170 , Brazil

Correspondence: Adriane Bello-Klein, Email: belklein{at}ufrgs.br

Abstract

This study was conducted to test whether oxidative stress activates the intracellular Akt signaling pathway, which culminates with cardiac hypertrophy in experimental hyperthyroidism. Male Wistar rats were divided into four groups: control, vitamin E, thyroxine (T4), and T4+vitamin E. Hyperthyroidism was induced by T4 administration (12 mg/L in drinking water for 28 days). Vitamin E treatment was given during the same period via subcutaneous injections (20 mg/kg/day). Morphometric and hemodynamic parameters were evaluated at the end of the 4 weeks treatment period. Protein oxidation, redox state (GSH/GSSG), vitamin C, total radical-trapping antioxidant potential (TRAP), hydrogen peroxide (H2O2), and nitric oxide metabolites (NOX) were measured in heart homogenates. The p-Akt/Akt ratio, p-GSK-3 beta/GSK-3 beta ratio, c-Fos, and c-Jun myocardial protein expression was also quantified by Western blot after four weeks. Increases in biochemical parameters, such as protein oxidation (41%), H2O2 (62%), NOX metabolites (218%), and increase in the left ventricular end diastolic pressure were observed in the T4 group. T4 treatment also caused a decrease in GSH/GSSG ratio (83%), in vitamin C (34%) and TRAP (55%). These alterations were attenuated by vitamin E administration to the hyperthyroid rats. Expression of p-Akt/Akt, p-GSK-3 beta/GSK-3 beta, and c-Fos, c-Jun were elevated in T4 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 Akt and c-Jun/c-Fos signaling pathways with H2O2 acting as possible intracellular mediator in this adaptive response to experimental hyperthyroidism.