Protein Synthetic Activity of Heart Microsomes and Ribosomes during Left Ventricular Hypertrophy in Rabbits

Abstract

Certain aspects of cytoplasmic protein synthesis have been studied during the early stages (0 to 5 days) of left ventricular hypertrophy produced by supravalvular constriction of the ascending aorta in adult rabbits. At 5 days after constriction, cell-free protein synthesis by microsomal preparations from hypertrophied heart muscle was increased, both from free phenylalanine or leucine (50 to 130*), and from phenylalanyl-soluble RNA, both with (70 to 250%) or without (70 to 150SS) polyuridylic acid as artificial messenger. Such increased activity was observed as early as 24 hr, and persisted to 5 days (the limit of the study). Sham preparations also displayed increased activity at 24 hr, which subsided by 5 days. The increased activity could be localized to the microsomal fraction: no differences were found when soluble fractions from normal, sham, and hypertrophied hearts, or from liver, were interchanged. Ribosomes from hypertrophied hearts were no more active than normal ribosomes. Increased yields of microsomal, ribosomal, and soluble RNA were found. It is suggested that the increased protein synthesis occurring in hypertrophy is localized in the microsomes, that soluble factors are not of major significance, and that an increased number of ribosomes (and microsomes) play a major role.ADDITIONAL KEY WORDS thyroid ribosomal RNA transfer enzymes transfer RNA soluble RNA aortic constriction activating enzymes polymerization factors• Hypertrophy is an increase in the mass of a tissue or organ without an increase in the number of cells in that organ. The demand for increased functional tissue is met by an increase in size and organelle content of preexisting cells, without parallel increases in cell number (1-3). This process, characterized by marked increases in tissue ribonucleic acid (RNA) and protein content in the face of minimal or no change in deoxyribonucleic acid (DNA) content, is of particular interest because it provides an opportunity From the Rockefeller University, New York, New York 10021.This investigation was supported by grants from the National Science Foundation and the U. S. Public Health Service.Dr. Moroz is a Fellow of the Helen Hay Whitney Foundation; his present address is Division of Immunochemistry and Allergy Research, Royal Victoria Hospital, Montreal 2, Canada.Accepted for publication August 21, 1967. to study accelerated protein synthesis uncomplicated by significant cellular proliferation. Typically, hypertrophy occurs in muscle, both skeletal and cardiac, and one of the most clear-cut experimental models is provided by the hypertrophy of the left ventricle of the heart subsequent to supravalvular constriction of the ascending aorta in mature animals. Such a preparation has been used to examine changes in the protein synthesizing apparatus of heart muscle during the early stages (0 to 5 days) of the hypertrophic process. A preliminary report of this work has appeared (4).

Myocardial Amino Acid Transport in the Isolated Rabbit Right Ventricular Papillary Muscle

“…XXVII, It has been demonstrated that rapid muscle growth is associated with an increase in the intracellular concentrations of free amino acids (13,14) as well as increased UNA synthesis and content, and increased rates of protein synthesis (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11). Whether the increased intracellular concentration of amino acids determines the increased rate of protein synthesis or is merely a consequence of enhanced substrate requirements is presently unclear (13,20,21).…”

“…• (dpm 1 4,-=-•C-AIB)/ml medium Inherent to the latter calculation is the assumption that the concentration of AIB in the extracellular fluid space and the medium are identical.…”

“…Anoxia does not inhibit this process whereas simultaneous inhibition of aerobic and anaerobic metabolism inhibits AIB accumulation. Intracellular AIB accumulation follows Michealis-Menten kinetics with a Km of 6.8 X ICHM and a V max of 6.6 fjt,mo\es • ml intracellular fluid -1 • hour" 1 . Sodium ion is obligatory for the transport process whereas no absolute potassium or calcium requirement exists.…”

“…Some of the biochemical characteristics of the hypertrophied heart have been described in the intact heart following banding of the aorta and pulmonary artery, or in an overloaded perfused heart Received February 25, 1970; accepted for publication July 7, 1970. preparation (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11). While the loading of the myocardium is altered by these techniques, their complexity does not permit a definition of the specific mechanical stimuli which induce hypertrophy.…”

Hemodynamic and Pathological Results from Experimentally Induced Left Ventricular Hypertrophy in the Rabbit

“…5907-02. used in small laboratory animals such as the guinea pig or rat as a method of inducing left ventricular hypertrophy [1, 4-7, 15, 20, 26]. Aortic constriction to produce hypertrophy in a larger animal such as the rabbit has been used predominantly in acute experiments [16,29]. M eerson's [12,13,14] extensive work in experimental cardiac hypertrophy and failure with the rabbit is well known.…”