Oxidative stress activates insulin-like growth factor I receptor protein expression, mediating cardiac hypertrophy induced by thyroxine.
Thyroxine can cause cardiac hypertrophy by activating growth factors, such as IGF-I (insulin-like growth factor-I). Since oxidative stress is enhanced in the hyperthyroidism, it would control protein expression involved in this hypertrophy. Male Wistar rats were divided into four groups: (I) control, (II) vitamin E-supplemented (20 mg/kg/day subcutaneous), (III) hyperthyroid (thyroxine 12 mg/l, in drinking water), and (IV) hyperthyroid + vitamin E. After 4 weeks, the contractility and relaxation indexes of left ventricle (LV), and cardiac mass were increased by 54%, 60%, and 60%, respectively, in hyperthyroid group. An increase in lipid peroxidation (around 40%), and a decrease in total glutathione (by 20%) was induced by thyroxine and avoided by vitamin E administration. Superoxide dismutase (SOD) and glutathione-S-transferase (GST) activities were increased (by 83% and 54%, respectively) in hyperthyroid, and vitamin E avoided changes in SOD. Protein expression of SOD, GST, and IGF-I receptor (IGF-IR) were increased (by 87%, 84%, and 60%, respectively) by thyroxine, and vitamin E promoted a significant reduction in SOD and IGF-IR expression (by 36% and 17%, respectively). These results indicate that oxidative stress is involved in cardiac hypertrophy, and suggest a role for IGF-IR as a mediator of this adaptive response in experimental hyperthyroidism.
Araujo
A S R
AS
Departamento Fisiologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Sarmento Leite, 500, 90050-170, Porto Alegre, RS, Brazil.
Enzveiler
A T
AT
Schenkel
P
P
Fernandes
T R G
TR
Ribeiro
M F M
MF
Partata
W A
WA
Llesuy
S
S
Belló-Klein
A
A
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001835:Body Weight; D006332:Cardiomegaly / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D013974:Thyroxine / Q000097:blood / Q000494:pharmacology*; D014810:Vitamin E / Q000494:pharmacology
D000975:Antioxidants; D014810:Vitamin E; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005982:Glutathione Transferase; D017526:Receptor, IGF Type 1; D005978:Glutathione; D013974:Thyroxine