Disproportionate reduction of actin synthesis in hearts of starved rats.

We examined the synthesis of proteins in rat myocardium after starvation. Rates of total protein synthesis in myofibrillar and nonmyofibrillar fractions of myocardium of starved animals were reduced similarly (to 70-80% of the rates in hearts of fed animals, p less than 0.002), but rates of synthesis of some individual proteins were affected discoordinately.

Influence of agents that alter lysosomal function on fetal mouse hearts recovering from anoxia and substrate depletion.

Recovery of fetal mouse heart myocytes from oxygen and substrate deprivation for 1 h is accompanied by complicated lysosomal and non-lysosomal vacuolar responses which can be subdivided temporally into four distinct phases that include production of lysosomal dense bodies; segregation of damaged subcellular organelles into vacuoles that initially lack lysosomal enzymes; delivery of lysosomal enzymes to these vacuoles through fusion with dense bodies, transforming them into lysosomal autophagic vacuoles and degradation of the sequestered organelles. These events are normally completed within 6 h of the resupply of oxygen and substrate. The progression of these events is influenced significantly by pharmacological interventions that alter lysosomal properties.

Lysosomal responses of fetal mouse hearts recovering from anoxia and substrate depletion.

Recovery from a 1 h period of anoxia and substrate deprivation is accompanied by a marked lysosomal response in myocytes of fetal mouse hearts maintained in organ culture. Two classes of subcellular vacuoles form within 5 to 15 min of recovery. One appears to provide lysosomal enzymes for degradation of subcellular particles, while the other segregates organelles within the cytoplasm of the injured myocyte.

Effects of glucocorticoid treatment on cardiac protein synthesis and degradation.

We treated rats with dexamethasone (DEX, 1 mg . kg-1 . day-1) and examined the effects of this glucocorticoid on heart protein metabolism using atrial explant and Langendorff perfusion preparations.

The role of lysosomes in the degradation of myofibrillar and non-myofibrillar proteins in heart.

Lysosomes are presumed to be involved in protein degradation in heart, but their exact role is poorly understood. Several interventions that are known to alter cardiac proteolysis (e.g.

The role of lysosomes and microtubules in cardiac protein degradation.

The mechanisms and regulatory factors involved in cardiac proteolysis are incompletely understood. Agents that interfere with lysosomal function (e.g.

Direct anabolic effects of thyroid hormone on isolated mouse heart.

The direct effects of L-and D-triiodothyronine (T3) on cardiac protein metabolism were investigated using fetal mouse hearts in organ culture. This model allowed the production of "thyrotoxicosis" in isolated hearts in vitro in the absence of the usual systemic metabolic and hemodynamic effects of thyroid hormones. Hearts were studied during the first 24 h of T3 exposure in culture, before changes in beating rate due to T3 occurred.

Changes in cardiac cathepsin B activity in response to interventions that alter heart size or protein metabolism: comparison with cathepsin D.

The specific activity of cardiac cathepsin B is significantly decreased by starvation and corticosteroid treatment in vivo, and by exposure of the heart in vitro to insulin, hydrocortisone and cycloheximide. Increases in cathepsin B activity occur following isoproterenol-induced cardiac damage in vivo and exposure in vitro to sucrose. Cathepsin B activity in heart is not changed during normal aging or in thyrotoxicosis.

Influence of chlorpromazine on lysosomal alterations during myocardial ischaemia.

Ligation of the circumflex artery of anaesthetised, open-chest rabbits caused a progressive increase in nonsedimentable cathepsin D activity in severely ischaemic myocardium and an anatomical redistribution of the enzyme from lysosomes into the cytosol, along with progressive ultrastructural signs of cellular damage and necrosis. Chlorpromazine pretreatment (15 mg X kg-1 intravenously) reduced the increase in nonsedimentable cathepsin D activity slightly, but no appreciable protective effect on the anatomical redistribution of the enzyme or the development of ultrastructural signs of necrosis could be detected. It is concluded that in this experimental model of myocardial infarction, high concentrations of chlorpromazine have a mild stabilising action on lysosomes, but the drug has minimal if any effect in protecting the heart from ischaemic damage.

Inhibition of cardiac proteolysis by colchicine. Selective effects on degradation of protein subclasses.

1. The effect of colchicine (2.5 microM) on cardiac protein turnover was tested with foetal mouse hearts in organ culture.

Mechanisms of degradation of myofibrillar and nonmyofibrillar protein in heart.

The degradation of cardiac proteins is known to be altered by many physiological and pathological interventions, but the precise intracellular processes that regulate proteolysis and the relative roles of different proteolytic pathways in degrading different classes of protein remain poorly understood. Agents that interfere with lysosomal function produce major decreases in total protein breakdown; thus, lysosomes and lysosomal proteinases seem to be important in proteolysis. However, these same agents cause no change in the degradation of myofibrillar proteins, suggesting that this class of proteins is not dependent on lysosomal pathways for its turnover.

Intracellular disruption of rat heart lysosomes by leucine methyl ester: effects on protein degradation.

Perfusion of rat hearts with Krebs--Henseleit medium containing 10 mM L-leucine methyl ester leads to swelling of lysosomes and loss of lysosomal integrity within 30-60 min. No morphological changes can be detected in the nuclei, mitochondria, sarcoplasmic reticulum, or Golgi complex as a result of the treatment with leucine methyl ester, and the hearts continue to beat normally during the treatment period. Homogenates of rat hearts perfused with the methyl ester exhibit a decrease in the sedimentability of cathepsin D activity compared to controls, thus providing additional evidence for a loss of lysosomal integrity.

Lysosomal alterations in heart, skeletal muscle, and liver of hyperthyroid rabbits.

Daily administration of L- or D-thyroxine for 1 week produced hypertrophy of the heart and atrophy of skeletal muscle and liver. The myocardial hypertrophy was accompanied by a rise in the activity of cathepsin D but not of cathepsin B; this was correlated with an increase in cathepsin-D-rich interstitial cells while the number of cathepsin-D-positive lysosomes in myocytes was decreased, as assessed from immunohistochemistry. In atrophying skeletal muscle (soleus and tibialis anterialis), large increases in the activities of cathepsins B and D were present.

Resistance to ischemic damage in hearts of starved rabbits: Correlation with lysosomal alterations and delayed release of cathepsin D.

Prolonged starvation produces dramatic changes both in the lysosomal properties of the heart and in its energy stores and, therefore, might be expected to alter some of the characteristic cardiac responses to ischemia. To test this possibility we ligated the circumflex coronary artery of rabbits that had been fed normally or starved for 6 days. Ultrastructural evidence of myocytic damage following 30 to 120 minutes of ischemia was much less severe in the starved animals than in the normally fed group.

Lysosomal alterations in hypoxic and reoxygenated hearts. I. Ultrastructural and cytochemical changes.

Rabbit hearts perfused under hypoxic conditions underwent progressive subcellular damage, which becomes irreversible by one hour. During the first 20 minutes of perfusion, minor dilation of mitochondria and condensation of nuclear chromatin were the only salient features of cell injury. By 40 minutes moderate mitochondrial swelling was evident in hypoxic myocytes.