Synthesis and degradation of myocardial protein during the development and regression of thyroxine-induced cardiac hypertrophy in rats.

Sanford, C. F.; Griffin, Edmond E.; Wildenthal, K.

doi:10.1161/01.res.43.5.688

Cited by 111 publications

(35 citation statements)

References 32 publications

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“…If, in contrast, T4 stimulates heart growth through changes in cardiovascular hemodynamics, then the in situ, but not the transplanted, heart should be so affected. The results of the present studies clearly show that, as in previous reports, thyroid hormone causes a marked increase in the heart weight and protein content ofthe in situ working heart (5). In contrast, thyroid hormone treatment did not increase the heart weight, left ventricular weight, total heart protein, or left ventricular protein in the hejerotopically transplanted nonworking heart.…”

Section: Discussionsupporting

confidence: 88%

“…A 100-mg portion of LV was homogenized in 7 ml of a buffer containing 40 mM NaCl and 3 mM Na2 HPO4 at pH 7.0 in a Potter-Elvehjem homogenizer (Kontes Co., Vineland, NJ) and centrifuged at 800 g for 10 min. The pellet was washed once in an equal volume ofthe same buffer, and then resuspended in 3 ml of a myosin extraction buffer containing 100 mM Na4 P207, 5 mM EGTA, 5 mM dithiothreitol, 5 mM ATP, 5 mM MgCl2, and 5 Ug/ ml leupeptin at pH 8.6. The homogenate was extracted at 3°C for 1 h and then centrifuged at 100,000 g for I h. After removing an aliquot for isoenzyme analysis, the supernatant was dialyzed overnight at 3°C against 1. Abbreviations used in this paper: bpm, beats per minute; LV(s), left ventricle(s); P, protein; Pi, inorganic phosphate; T3, triiodothyronine; T4, I-thyronine.…”

Section: Methodsmentioning

confidence: 99%

“…Previous studies have shown that administration of excess thyroid hormone leads to increased synthesis of RNA, increased protein synthesis, and the development of cardiac hypertrophy (4,5). These changes in the myocardial protein synthesis occur in association with an increased heart rate, cardiac output, increased myocardial contractility, and the development of cardiac hypertrophy (1,3,6).…”

Section: Introductionmentioning

confidence: 99%

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Effects of thyroid hormone on cardiac size and myosin content of the heterotopically transplanted rat heart.

Klein¹,

Hong²

1986

J. Clin. Invest.

165

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Infrarenal heterotopic cardiac isografts maintain structural and functional integrity. We have used this transplantation model to further explore the mechanisms of thyroid hormone-induced cardiac hypertrophy. Thyroid hormone administration, 1-thyroxine (T4) 10 Mg/animal per d, led to a significant 30% increase in total heart weight and a 40% increase in the myosin content of the in situ heart when compared with control. In contrast, T4 treatment was without effect on the heart weight, protein content, rate of protein synthesis, or calculated myosin content of the heterotopic, nonworking heart. Heterotopic hearts demonstrated a significant decrease in the percentage of the VI myosin isoenzyme from 95% to 61%. This shift occurred in euthyroid animals but was prevented by T4 treatment. These results suggest that thyroxine-induced cardiac hypertrophy is mediated indirectly via changes in cardiac work. Myosin isoenzyme expression can be altered by changes in work load but is still responsive to increased levels of thyroid hormone.

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Section: Discussionsupporting

confidence: 88%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effects of thyroid hormone on cardiac size and myosin content of the heterotopically transplanted rat heart.

Klein¹,

Hong²

1986

J. Clin. Invest.

165

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“…When hypertrophy occurs, the myocardium is more susceptible to hypoxia (Taylor, 1970), and myocardial contractility and relaxation are impaired (Palacios et al, 1979), so that isolated perfused heart preparations would be less viable. However, some cardiac hypertrophy has been shown to occur as early as three days after starting T4 treatment (Sanford et al, 1978). Thus, the 18% increase in heart weight observed in the T4-treated rats in the present study was not unexpected.…”

Section: Discussionsupporting

confidence: 56%

The effects of thyroxine treatment of rats on neuronal and extraneuronal uptake and metabolism of catecholamines in the heart

Bryan

O’Donnell

Williams

1986

British J Pharmacology

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1 The effects of thyroxine (T4) treatment of rats on the neuronal and extraneuronal uptake and subsequent metabolism ofcatecholamines in the heart were examined, to determine whether changes in the local dissipation of catecholamines might contribute to the enhanced sympathetic cardiac responses that occur when thyroid hormone levels are elevated. 2 T4-treated rats were injected subcutaneously with L-thyroxine sodium 1 mg kg-' on days 1, 3 and 5, and controls were injected with the normal saline vehicle on the same days. The experiments on isolated, perfused hearts were carried out on day 8. The T4-treated rats had only 50% of the growth rate ofthe controls and their heart weights were 18% greater than the controls. The experimental data were adjusted to allow for the increase in heart weight caused by the T4 treatment. 3 The initial rates ofneuronal uptake ofnoradrenaline and ofextraneuronal uptake ofnoradrenaline and isoprenaline in the hearts from T4-treated rats were not significantly different from those in hearts from control rats. 4 The steady-state rates of extraneuronal O-methylation of isoprenaline and of extraneuronal deamination of noradrenaline in hearts from T4-treated rats were not significantly different from those in hearts from control rats. 5 The steady-state rate of neuronal deamination of noradrenaline was significantly lower and the accumulation of unmetabolized noradrenaline in the hearts was significantly greater in T4-treated rats than in the controls. These findings could be explained by a decrease in neuronal monoamine oxidase activity or by an increase in intraneuronal binding of noradrenaline in hearts from T4-treated rats. If the first of these two speculations should be correct, the changes in neuronal dissipation could contribute to cardiac supersensitivity to noradrenaline or adrenaline, since these amines are substrates for neuronal uptake. However, it could not explain cardiac supersensitivity to isoprenaline in T4-treated rats. 6 The study has shown that it is unlikely that increased plasma thyroid hormone levels cause cardiac supersensitivity to catecholamines by affecting the local dissipation processes for those amines in the heart.

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“…These changes in isozyme pattern must represent prior changes in rates of synthesis or degradation. In the case of the heart, available evidence indicates that hypertrophic growth is a product of increased protein synthesis rather than decreased protein degradation (24). Therefore, it seems likely that changes in isozyme pattern as well as hypertrophy result from alterations in RNA transcription leading to changed or increased protein synthesis.…”

Section: Resultsmentioning

confidence: 99%

Molecular signals for initiating protein synthesis in organ hypertrophy.

Hammond¹,

Wieben²,

Markert³

1979

Proc. Natl. Acad. Sci. U.S.A.

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When chronically provoked to increased physiologic activity, organs increase in mass through augmented protein synthesis. This process of compensatory hypertrophy can involve cell division as well as cell growth. To test for molecules that might regulate organ size, by inducing hypertrophy, we performed a series of experiments using isolated, perfused, canine hearts in which theleft ventricle was beating but performed no work. Hypertrophying hearts and kidneys as well as normal control organs were extracted and the extracts were perfused through isolated heart preparations. Before and after perfusion, RNA was extracted from fragments of the isolated hearts and translated in cell-free media containing [3sSlmethi-onine. Incorporation of methionine into protein was measured by liquid scintillation spectrometry. WCen erfused through normal hearts, extracts from hypertrophying heart and kidney were able to increase greatly the translational ability of RNA extracted from the normal hearts; corresponding perfusates from nonhypertrophying hearts and kidneys had no effect. Our results indicate that molecules that initiate hypertrophic organ growth are extractable, are generated by the cells of the organ under stress, and are probably similar in heart and kidney and perhaps in many other organs as well. When stimulated to increased function, many organs respond by growing larger. Such growth may involve hypertrophy (increased cell size) or hyperplasia (increased cell division) or both (1). The initial stimulus to growth may be mediated through the nervous (2) or endocrine (3) system or by chemical changes produced by the stressed cells themselves. Determination of organ size is critically important to the structure and function of an organism, and the problem of hypertrophic growth regulation has attracted the attention of investigators for many years.Several hypotheses can be advanced to account for the regulation of organ size: (i) stimulating or inhibiting molecules released by the target organ and acting in feedback loops upon the organ have often been suggested as a basic mechanism for fixing organ size in accord with the physiological needs of the organism (4, 5); (ii) growth may occur as a consequence of the production of specific kinds of molecules (6, 7) within the target cells themselves without the involvement of any circulating molecules; (iii) shifting patterns of metabolic events may bring functional activity and size into concordance, with changes in the proportions of existing molecular species but without the production of regulatory molecules (8, 9). In an attempt to test these various hypotheses and to discover substances that might be involved in regulating organ size, we performed a series of experiments using the canine heart as a target organ.The muscle cells of mammalian hearts do not increase in number after birth, but they do increase in size in response to increased work loads-that is, the heart hypertrophies. An early biochemical indication of impending hypertrophy is increased RNA synt...

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Synthesis and degradation of myocardial protein during the development and regression of thyroxine-induced cardiac hypertrophy in rats.

Cited by 111 publications

References 32 publications

Effects of thyroid hormone on cardiac size and myosin content of the heterotopically transplanted rat heart.

Effects of thyroid hormone on cardiac size and myosin content of the heterotopically transplanted rat heart.

The effects of thyroxine treatment of rats on neuronal and extraneuronal uptake and metabolism of catecholamines in the heart

Molecular signals for initiating protein synthesis in organ hypertrophy.

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