Thyroid hormone regulation of phospholamban phosphorylation in the rat heart
Abstract
Thyroid hormone exerts predictable effects on the contractile performance of the heart in part by regulating the transcription of genes encoding specific calcium transporter proteins. In a rat model of hypothyroidism, left ventricular (LV) contractile function as measured by ejection fraction was decreased by 22% (P < 0.05), and this was returned to control values with T3 treatment. In confirmation of prior studies, LV phospholamban (PLB) protein content was significantly decreased by 25% and 40% compared with hypothyroid LV when the animals were treated with T3 at two doses, 2.5 and 7.0 μg/day, respectively. The ratio of sarcoplasmic reticulum calcium adenosine triphosphatase (SERCA2) to PLB protein content was thus increased by 171% and 207%, respectively (P < 0.01). Resolution of the phosphorylated PLB pentamers by SDS-PAGE showed that T3 infusion at 2.5 and 7.0 μg/day decreased (P < 0.001) the amount nonphosphorylated pentamers by 82% and 95%, respectively, in a dose-dependent manner. T3 treatment produced an increase in the proportion of highly phosphorylated PLB pentamers (more than five phosphates) when expressed as a fraction of total pentameric molecules (P < 0.05). Site-specific antibodies showed that the T3-induced increase in phosphorylated PLB pentamers was the result of an increase in both serine 16 and threonine 17 phosphorylation. We conclude that thyroid hormone, in addition to regulating the expression of cardiac PLB, is able to alter the degree of PLB phosphorylation, which correlates with enhancement of LV contractile function. These studies suggest that T3 may augment myocyte calcium cycling via changes in both cAMP- and calcium/calmodulin-dependent protein kinase activities.
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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 Ojamaa, et al., 2000
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- Authors
- Ojamaa, K., Kenessey, A., & Klein, I.
- Affiliations
- North Shore University Hospital (US)
- Department of Medicine, Division of Endocrinology, North Shore University Hospital; and Departments of Medicine and Cell Biology, New York University School of Medicine, Manhasset, New York 11030
- Corresponding author
- Ojamaa, Kaie
- ORCID
- Ojamaa, Kaie
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2000-06-01
- Volume
- 141
- Issue
- 6
- Pages
- 2139-2144
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2124633479
- Cited by
- 106
- References
- 25
- Citations by year
- 2024: 3 · 2022: 1 · 2021: 6 · 2020: 4 · 2019: 5 · 2018: 6 · 2017: 2 · 2016: 6 · 2015: 2 · 2014: 7 · 2013: 4 · 2012: 6
- FWCI
- 3.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5k02hl003775-05, 5r01hl058849-03)
- National Heart, Lung, and Blood Institute (R01HL056804, HL03775, HL-56804, HL58849)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Keywords
- thyroid hormones, triiodothyronine, phospholamban, phospholamban phosphorylation, hypothyroidism, left ventricular contractility, SERCA2, sarcoplasmic reticulum calcium ATPase, calcium handling, protein kinase A, calcium/calmodulin-dependent protein kinase, cardiomyocytes, ejection fraction
- MeSH terms
- Phospholamban, Calcium-Transporting ATPases, Animals, Calcium-Binding Proteins, Hypothyroidism, Male, Myocardial Contraction, Myocardium, Phosphorylation, Propylthiouracil, RNA, Messenger, Sarcoplasmic Reticulum, Triiodothyronine, Rats, Sprague-Dawley, Rats
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