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M-Protein Is Down-Regulated in Cardiac Hypertrophy Driven by Thyroid Hormone in Rats
- Source :
- Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual), Universidade de São Paulo (USP), instacron:USP
- Publication Year :
- 2013
- Publisher :
- Endocrine Society, 2013.
-
Abstract
- Although it is well known that the thyroid hormone (T3) 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 T3 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 T3. Real-time quantitative PCR-based measurements confirmed that T3 (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, T3 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 T3, 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 T3. We concluded that the M-protein expression is strongly and rapidly repressed by T3 in cardiomyocytes, which represents an important aspect for the basis of T3-dependent sarcomeric deleterious effects in the heart.
- Subjects :
- Cardiac function curve
Male
Sarcomeres
medicine.medical_specialty
Thyroid Hormones
Molecular Sequence Data
Down-Regulation
Cardiomegaly
Cell Line
Mice
Endocrinology
Downregulation and upregulation
Hypothyroidism
Internal medicine
Gene expression
medicine
Animals
Connectin
Myocytes, Cardiac
RNA, Messenger
Rats, Wistar
Promoter Regions, Genetic
Molecular Biology
Cells, Cultured
Original Research
Oligonucleotide Array Sequence Analysis
Triiodothyronine
Receptors, Thyroid Hormone
biology
Base Sequence
Microarray analysis techniques
Thyroid
General Medicine
ANATOMIA
Myocardial Contraction
Rats
Up-Regulation
medicine.anatomical_structure
Thyrotoxicosis
Animals, Newborn
biology.protein
Titin
Hormone
Protein Binding
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual), Universidade de São Paulo (USP), instacron:USP
- Accession number :
- edsair.doi.dedup.....d4f2667e044827a43aff9afea4d4faef