Regulation of myosin synthesis by thyroid hormone: relative change in the .alpha.- and .beta.-myosin heavy chain mRNA levels in rabbit heart

Abstract

The expression of mRNAs for two cardiac myosins has been examined in the ventricles of hypo- and hyperthyroid rabbits by means of cloned cDNA sequences corresponding to the mRNAs of the alpha- and beta-myosin heavy chains (HCs). The temporal change in the relative levels of the alpha- and beta-HC mRNAs after 3,5,3'-triiodothyronine (T3) treatment of hypothyroid rabbits was determined by nuclease S1 mapping. In the hypothyroid state, only HC beta-mRNA was expressed in the ventricles. The HC alpha-mRNA was first detectable 4 h after administration of T3 (200 micrograms/kg) to hypothyroid animals. By 12 h, HC alpha-mRNA represented 20% of total myosin mRNA, increasing to 50% by 24 h and to about 90% by 72 h. The relationship between the relative mRNA levels and relative synthesis rates of the myosin HCs was evaluated in 5-6-week-old normal and thyrotoxic rabbits. Myosin synthesis rates were determined by labeling of protein in vivo with [3H]leucine. The V1 (HC alpha) and V3 (HC beta) isomyosins were separated by affinity chromatography with monoclonal antibodies, and the HCs were isolated electrophoretically. In a normal euthyroid group of animals and in animals 12 and 24 h after administration of 200 micrograms of 3,5,3',5'-tetraiodothyronine/kg, the relative mRNA levels and relative synthesis rates of the alpha- and beta-HCs were not significantly different. Our results show that, first, thyroid hormone causes a rapid accumulation of HC alpha-mRNA and loss of HC beta-mRNA and, second, in normal and thyrotoxic rabbits, the relative synthesis rates of HC alpha and HC beta reflect the relative abundance of the alpha- and beta-HC mRNAs.(ABSTRACT TRUNCATED AT 250 WORDS)

Myosin heavy chain messenger RNA and protein isoform transitions during cardiac hypertrophy. Interaction between hemodynamic and thyroid hormone-induced signals.

“…We and others have previously shown that the cardiac MHC isozyme transition during normal development and thyroid hormone manipulation is regulated by changes in the levels of the respective mRNAs (20,33), which in turn appear to be transcriptionally regulated. Furthermore, the preliminary results of nuclear run-off experiments suggest that thyroid hormone regulates the a-and ,B-MHC genes at the level oftranscription, and not by changes in mRNA half-life (34).…”

Factors controlling cardiac myosin-isoform shift during hypertrophy and heart failure

“…Proteolytic fragment S1, corresponding to myosin head domain and two other proteolytic fragments, S2 and LMM (light meromyosins) corresponding to alpha-helical rod domain are shown. (C) Schematic representation of the developmental regulation of rat and rabbit heart myosin isoforms during fetal, adult and old age of the animal [15,16,154]. Increased activity of PARP1 in physiologic and pathologic hypertrophy.…”

Hyperthyroidism selectively modified a transient potassium current in rabbit ventricular and atrial myocytes.

“…Overall, protein synthesis is enhanced (Michels, Cason & Sokoloff, 1963), with an increase in oxidative metabolism and glycolytic capacity (Seymour, Eldar & Radda, 1990). The improvement in cardiac performance is largely due to shifts in myosin isoform distribution, so that the V1 form predominates (Dillmann, 1984;Everett et al 1984). The faster ATPase action of this isoform underlies the enhanced speed of contraction.…”