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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

M-Protein Is Down-Regulated in Cardiac Hypertrophy Driven by Thyroid Hormone in Rats

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Author(s):
Rozanski, Andrei [1, 2] ; Takano, Ana Paula C. [2] ; Kato, Patricia N. [2] ; Soares, Antonio G. [3] ; Lellis-Santos, Camilo [4] ; Campos, Juliane Cruz [2] ; Batista Ferreira, Julio Cesar [2] ; Barreto-Chaves, Maria Luiza M. [2] ; Moriscot, Anselmo S. [2]
Total Authors: 9
Affiliation:
[1] Univ Sao Paulo, Inst Biomed Sci, Dept Cell & Dev Biol, BR-05508900 Sao Paulo - Brazil
[2] Univ Sao Paulo, Inst Biomed Sci, Dept Anat, BR-05508900 Sao Paulo - Brazil
[3] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, BR-05508900 Sao Paulo - Brazil
[4] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, BR-05508900 Sao Paulo - Brazil
Total Affiliations: 4
Document type: Journal article
Source: MOLECULAR ENDOCRINOLOGY; v. 27, n. 12, p. 2055-2065, DEC 2013.
Web of Science Citations: 2
Abstract

Although it is well known that the thyroid hormone (T-3) is an important positive regulator of cardiac function over a short term and that it also promotes deleterious effects over a long term, the molecular mechanisms for such effects are not yet well understood. Because most alterations in cardiac function are associated with changes in sarcomeric machinery, the present work was undertaken to find novel sarcomeric hot spots driven by T-3 in the heart. A microarray analysis indicated that the M-band is a major hot spot, and the structural sarcomeric gene coding for the M-protein is severely down-regulated by T-3. Real-time quantitative PCR-based measurements confirmed that T-3 (1, 5, 50, and 100 physiological doses for 2 days) sharply decreased the M-protein gene and protein expression in vivo in a dose-dependent manner. Furthermore, the M-protein gene expression was elevated 3.4-fold in hypothyroid rats. Accordingly, T-3 was able to rapidly and strongly reduce the M-protein gene expression in neonatal cardiomyocytes. Deletions at the M-protein promoter and bioinformatics approach suggested an area responsive to T-3, which was confirmed by chromatin immunoprecipitation assay. Functional assays in cultured neonatal cardiomyocytes revealed that depletion of M-protein (by small interfering RNA) drives a severe decrease in speed of contraction. Interestingly, mRNA and protein levels of other M-band components, myomesin and embryonic-heart myomesin, were not altered by T-3. We concluded that the M-protein expression is strongly and rapidly repressed by T-3 in cardiomyocytes, which represents an important aspect for the basis of T-3-dependent sarcomeric deleterious effects in the heart. (AU)