![]() ![]() ROS are integral to the induction and maintenance of many signal transduction pathways involved in cell growth and differentiation ( Valko et al. In a previous study, we demonstrated a positive correlation between cardiac hypertrophy and oxidative stress in experimental hyperthyroidism, indicating that reactive oxygen species (ROS) may contribute to the progression to heart failure in this model ( Araujo et al. Although cardiomyocyte growth can be a beneficial adaptation, chronic exposure to such stimuli can lead to maladaptive hypertrophy resulting in dilated cardiomyopathy and heart failure ( Li et al. 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 H 2O 2 acting as a possible intracellular mediator in this adaptive response to experimental hyperthyroidism.Ĭardiac hypertrophy is an adaptive response to a variety of stimuli, including volume and pressure overload and neurohormonal activation ( Donatelli et al. 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 alterations were attenuated by vitamin E administration to the hyperthyroid rats. T 4 treatment also caused a decrease in GSH/GSSG ratio (83%), vitamin C (34%), and TRAP (55%). Increases in biochemical parameters, such as protein oxidation (41%), H 2O 2 (62%), and NO X (218%), and increase in the left ventricular end-diastolic pressure were observed in the T 4 group. 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. Protein oxidation, redox state (reduced glutathione, GSH/glutathione dissulfide, GSSG), vitamin C, total radical-trapping antioxidant potential (TRAP), hydrogen peroxide (H 2O 2), and nitric oxide metabolites (NO X) were measured in heart homogenates. Morphometric and hemodynamic parameters were evaluated at the end of the 4-week treatment period. Vitamin E treatment was given during the same period via s.c. Hyperthyroidism was induced by T 4 administration (12 mg/l in drinking water for 28 days). Male Wistar rats were divided into four groups: control, vitamin E, thyroxine (T 4), and T 4+vitamin E. 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. ![]()
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