Thyroid hormone inhibits ERK phosphorylation in pressure overload-induced hypertrophied mouse hearts through a receptor-mediated mechanism
Open accessAbstract
Pressure overload-induced cardiac hypertrophy results in a pathological type of hypertrophy with activation of signaling cascades like the extracellular signal-regulated kinase (ERK) pathway, which promotes negative cardiac remodeling and decreased contractile function. In contrast, thyroid hormone mediates a physiological type of hypertrophy resulting in enhanced contractile function. In addition, thyroid hormone action is diminished in pressure overload-induced cardiac hypertrophy. We hypothesized that thyroid hormone status modulates ERK activity and that administration of thyroid hormone could alter the activity of this kinase in cardiac hypertrophy induced by pressure overload. ERK is activated by phosphorylation; accordingly, we investigated phosphorylation of ERK in hearts of control, hypothyroid, and hyperthyroid mice. In addition, the effect of T3 treatment on ERK phosphorylation in hypertrophied hearts from transverse aortic-constricted (TAC) mice was investigated. Results showed that phosphorylated ERK (p-ERK) was decreased by 25% in hyperthyroid mice. In contrast, hypothyroid mice presented increased p-ERK by 80%. TAC mice presented a greater than fourfold increase of p-ERK compared with control mice. Interestingly, T3 administration dramatically canceled TAC-induced ERK phosphorylation (36% lower compared with control). Raf-1 is upstream of the ERK pathway. TAC mice presented a 45% increase in phospho-Raf-1 (Ser338). T3 treatment inhibited this effect of pressure overload and further decreased p-Raf-1 (Ser338) by 37%, compared with control. Overexpression of thyroid hormone receptor-α in cultured cardiomyocytes potentiated the inhibitory effect of T3 on ERK phosphorylation. We concluded that thyroid hormone has an inhibitory effect on the Raf-1/ERK pathway. Furthermore, treatment of TAC mice with T3 inhibited Raf-1/ERK pathway by a thyroid hormone receptor-dependent mechanism.
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Hypothyroidism in rats induces phosphorylation changes in some proteins.
“phosphorylation of some proteins (Ojamaa, Kenessey, & Klein, 2000; Suarez, Scott, Suarez-Ramirez, Chavira, & Dillmann, 2010; Tang, et al., 2005).”
From Small and large animal models in cardiac contraction research: advantages and disadvantages (2014) · cites this paper as Suarez, et al., 2010
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References 31 · Cited by 30
- Authors
- Suarez, J., Scott, B. T., Suarez-Ramirez, J. A., Chavira, C. V., & Dillmann, W. H.
- Affiliations
- Department of Medicine, University of California, San Diego, La Jolla, California
- University of California San Diego (US)
- Corresponding author
- Dillmann, Wolfgang H.
- Venue
- American Journal of Physiology-Cell Physiology
- Publisher
- American Physiological Society
- Published
- 2010-12
- Volume
- 299
- Issue
- 6
- Pages
- C1524-C1529
- ISSN
- 0363-6143 (ISSN-L)
- 1522-1563
- PMC
- PMC3006330
- OpenAlex
- W1967472603
- Cited by
- 30
- References
- 31
- Citations by year
- 2024: 2 · 2023: 3 · 2022: 2 · 2021: 4 · 2020: 3 · 2019: 2 · 2014: 3 · 2013: 6 · 2012: 3
- FWCI
- 2.42
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Physiology-Cell Physiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL-89938, R01HL089938)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Keywords
- thyroid hormones, triiodothyronine, ERK1/2 phosphorylation, Raf-1, cardiac hypertrophy, pressure overload, transverse aortic constriction, thyroid hormone receptor alpha, hypothyroidism, hyperthyroidism, cardiac remodeling, cardiomyocytes
- MeSH terms
- Animals, Blood Pressure, Cardiomegaly, Hyperthyroidism, Hypothyroidism, Male, Phosphorylation, Receptors, Thyroid Hormone, Triiodothyronine, Myocytes, Cardiac, Extracellular Signal-Regulated MAP Kinases, Mice, Rats
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