Redox regulation of myocardial ERK 1/2 phosphorylation in experimental hyperthyroidism: role of thioredoxin-peroxiredoxin system.
The present study was conducted to test whether adaptation in the antioxidant system would differentially modulate prosurvival and proapoptotic proteins in hyperthyroidism-induced cardiac hypertrophy. Male Wistar rats were divided into 4 groups: control, vitamin E (20 mg · kg(-1) · d(-1) subcutaneously, 28 days), thyroxine (T4) (12 mg/L in drinking water for 28 days), and T4 + vitamin E. Cardiac mass, redox ratio, glutathione peroxidase (GPx) and glutathione reductase (GR) activities, NF-E2-related factor 2 (Nrf2) thioredoxin-1 (Trx-1), peroxiredoxin-6 (Prx-6), phospho-extracellular-signal-regulated kinases 1/2 (p-ERK 1/2)/extracellular-signal-regulated kinases 1/2 (ERK1/2), and phospho-c-Jun N-terminal kinase (p-JNK)/c-Jun N-terminal kinase (JNK) myocardial protein expression were quantified. Cardiac hypertrophy was attenuated in the T4 + vitamin E group. The redox ratio; GPx and GR; as well as Nrf2, Trx-1, Prx-6, and p-ERK1/2/ERK1/2 immunocontent were elevated in T4 group. All these effects were attenuated by vitamin E administration. p-JNK/JNK remained unchanged in all the groups. The overall results suggest that redox imbalance due to hyperthyroidism induce adaptation of antioxidant systems, favoring ERK1/2 activation and leading to development of cardiac hypertrophy.
Araujo
Alex Sander da Rosa
AS
Department of Physiology, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Fernandes
Tania
T
Ribeiro
Maria Flavia
MF
Khaper
Neelam
N
Belló-Klein
Adriane
A
D000818:Animals; D006332:Cardiomegaly / Q000209:etiology / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D006980:Hyperthyroidism / Q000150:complications / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000502:physiology*; D048052:Mitogen-Activated Protein Kinase 3 / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D054464:Peroxiredoxins / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D013879:Thioredoxins / Q000378:metabolism*
D051267:NF-E2-Related Factor 2; D013879:Thioredoxins; D054464:Peroxiredoxins; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3