Protein synthesis and degradation during starvation-induced cardiac atrophy in rabbits.

Abstract

To determine the relative importance of protein degradation in the development of starvation-induced cardiac atrophy, in vivo fractional synthetic rates of total cardiac protein, myosin heavy chain, actin, light chain 1, and light chain 2 were measured in fed and fasted rabbits by continuous infusion of [3H] leucine. In addition, the rate of left ventricular protein accumulation and loss were assessed in weight-matched control and fasted rabbits. Rates of total cardiac protein degradation were then estimated as the difference between rates of synthesis and growth. Fasting produced left ventricular atrophy by decreasing the rate of left ventricular protein synthesis (34.8 +/- 1.4, 27.3 +/- 3.0, and 19.3 +/- 1.2 mg/day of left ventricular protein synthesized for 0-, 3-, and 7-day fasted rabbits, respectively). Inhibition of contractile protein synthesis was evident by significant reductions in the fractional synthetic rates of all myofibrillar protein subunits. Although fractional rates of protein degradation increased significantly within 7 days of fasting, actual amounts of left ventricular protein degraded per day were unaffected. Thus, prolonged fasting profoundly inhibits the synthesis of new cardiac protein, including the major protein constituents of the myofibril. Both this inhibition in new protein synthesis as well as a smaller but significant reduction in the average half-lives of cardiac proteins are responsible for atrophy of the heart in response to fasting.

Ventricular remodeling and diastolic myocardial dysfunction in rats submitted to protein-calorie malnutrition

“…Several authors have tried to explain LV wall thinning induced by malnutrition. These explanations included a failure to deliver the metabolic requirements to the myocardium (41), a decrease in the synthesis of myofibrillar component (36), and an increase in myofibrillar protein catabolism (51). LV chamber enlargement and wall thinning has also been described in dogs (2, 3) and humans (34,37) with malnutrition.…”

Differential Regulation of MAPK Isoforms during Cast-Immobilization -Induced Atrophy in Rat Gastrocnemius Muscle

“…Increased muscle loading during activity or physical exercise triggers signaling events that induce muscle hypertrophy. Likewise, decreased loading due to inactivity, malnutrition, food deprivation, or muscle injury triggers signaling pathways that induce skeletal muscle atrophy [15][16][17] . Skeletal muscle atrophy has been widely reported to be related to nutrient-deprivation conditions such as cell starvation and depletion of amino acids [17][18][19] .…”

“…Likewise, decreased loading due to inactivity, malnutrition, food deprivation, or muscle injury triggers signaling pathways that induce skeletal muscle atrophy [15][16][17] . Skeletal muscle atrophy has been widely reported to be related to nutrient-deprivation conditions such as cell starvation and depletion of amino acids [17][18][19] . In this study, we confirmed that cast immobilization of rat gastrocnemius muscles significantly decreases the muscle weight, the muscle weight-to-body weight ratio, and the muscle cross-sectional area.…”

Estudo morfométrico do miocárdio em adultos com subnutrição protéico-energética

“…Tal fato não está de acordo com a maior relação peso cardíaco/peso corporal observada em indivíduos subnutridos, que sugere relativa preservação do peso cardíaco em relação à intensidade do emagrecimento corporal. A menor espessura dos miocardiócitos de indivíduos subnutridos está de acordo com a hipotrofia miofibrilar observada em animais, causada pela diminuição da síntese de componentes das miofibrilas 13 e aumento do catabolismo protéico miofibrilar, secundário ao aumento da atividade das proteinases lisossômicas 14 . A similitude das dimensões nucleares de subnutridos e controles sugerem também a manutenção do potencial recuperativo do coração.…”

“…No presente trabalho, documentou-se menor espessura de miocardiócitos em indivíduos com subnutrição de grau avançado, fenômeno que talvez reflita o predomínio do catabolismo protéico sobre os processos anabólicos 13 . Estas alterações morfo-funcionais miocárdicas poderiam se manifestar clinicamente como ICC e arritmias cardíacas 17 , intercorrências comuns em pacientes terminais.…”