title: Redox regulation of myocardial ERK 1/2 phosphorylation in experimental hyperthyroidism: role of thioredoxin-peroxiredoxin system.
abstract: 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.
authors: Department of Physiology, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors: Alex Sander da Rosa
authors: AS
authors: Araujo
authors: Tania
authors: T
authors: Fernandes
authors: Maria Flavia
authors: MF
authors: Ribeiro
authors: Neelam
authors: N
authors: Khaper
authors: Adriane
authors: A
authors: Belló-Klein
mesh_terms: 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*
chemical_list: 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