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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of a six day starvation regimen on rats' hearts were studied by electron microscopy in combination with marker-enzyme assays of density-sedimentation (rho-S) zonal centrifugation fractions, and with Na+, K+ and Ca++ determinations of sera and heart homogenates. The evidence suggested that massive intracellular cardiac destruction occurred by two pathways. One pathway was seen by electron micrography in which proliferation of lysosomal populations was demonstrated. The finding was confirmed biochemically by increased activities of lysosomal acid hydrolases, particularly cathepsin D. The second pathway was deduced from biochemical and electrolytic data. It was believed to have been initiated by cellular K+ retention, which provided the acid milieu required for intracellular Ca++ retention. It is postulated that the resulting increase in Ca++ activated the loosely-bound membrane neutral (pH 7.4), and alkaline (pH 8.5) proteases, causing subcellular autolysis, particularly involving mitochondria, myofibrils and sarcoplasmic reticulum.
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PMID:Effects of starvation on vacuolar apparatus of cardiac muscle tissue determined by electron microscopy, marker-enzyme assays and electrolyte studies. 61 Oct

Prolonged starvation is known to induce significant alterations in several cardiac lysosomal enzymes, particularly the acid proteinase cathepsin D. To determine what specific factors might mediate these changes, fetal mouse hearts in organ culture were maintained in media designed to simulate selected hormonal or nutritional substrate changes that accompany starvation. Reduced concentrations of glucose caused an increase in the activity of beta-acetylglucosaminidase but had no effect on cathepsin D or acid phosphatase activites (i.e., effects opposite from those of starvation). Also, high concentrations of free fatty acid, acetoacetate, and beta-OH-butyrate induced an increase in cathepsin D (+18%) and a simultaneous decrease in glucosaminidase (-19%), with little change in acid phosphatase. Furthermore, glucagon had no effect on any of the enzymes, whereas growth hormone caused a small (6%) increase in cathepsin D activity. In addition, insulin deprivation caused significant increases (7-25%) in the activities of all three enzymes. Insulin deprivation and excess ketones, but not the other interventions, increased the proportion of enzyme activity which was nonsedimentable. These results suggest the possibility that lysosomal alterations during starvation may be related in part to prolonged insulin deficiency and exposure to high concentrations of ketones and free fatty acids.
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PMID:Hormonal and nutritional substrate control of cardiac lysosomal enzyme activities. 95 75

Prolonged starvation in rats is accompanied by consistent increases in the total cardiac activity and the nonsedimentable activity of cathepsin D, the major detectable lysosomal acid proteinase in the heart. Fluorescent staining of rabbit hearts with specific anticathepsin D antiserum reveals that the increase occured predominantly in myocytes, but increased formation of autophagic vacuoles cannot be demonstrated in the myocardial cells by electron microscopy. No changes in cathepsin D occur in animals fed pure carbohydrate or pure fat diets for similar periods, indicating that it is caloric deficiency and not dietary protein deficiency that alters catheptic activity. At the same time that cardiac cathepsin D activity increases markedly, acid phosphatase increases slightly, and the activity of beta-acetyl-glucosaminidase is significantly lower than in hearts of fed rats. The data are compatible with the hypothesis that increased activity of lysosomal acid proteinase may contribute to the net protein catabolism and cardiac atrophy that accompany starvation, especially late in the period of food deprivation. A generalized activation of all lysosomal enzymes does not occur with starvation, however, and the activities of some lysosomal enzymes in the heart decrease.
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PMID:Dietary control of cardiac lysosomal enzyme activities. 121 47

Autophagic vacuoles (AVs) arise when membranes of the ER sequester parts of the cytoplasm, forming a new, double-membraned vacuole, to which lysosomal enzymes are then delivered. To investigate the mechanism of lysosomal enzyme delivery to nascent AVs, amino acid (AA) starvation and glucagon treatment were used to induce autophagy in a cultured cell system using rat hepatocytes (Fu5C8 cells). The induction of autophagy was assayed using biochemical, morphometric and immunocytochemical techniques. In these cells, AA starvation resulted in a fivefold increase in total cellular proteolysis, and sixfold and 4.5-fold increases in the volume and surface densities of AVs, respectively. Using an antibody against the mannose 6-phosphate receptor (MPR) and two sizes of colloidal gold to label separately and track the endosomal and lysosomal compartments, the time course of endosomal and lysosomal fusion with AVs was analyzed in detail. On the basis of these experiments, we found that AVs rapidly fuse with pre-existing lysosomes, but seldom with a prelysosomal compartment (PLC). Using immunoperoxidase, staining for the MPR was infrequently observed in association with any AVs. However, at early times following the induction of autophagy (less than 2 h), many autophagic vacuoles stained positively for the lysosomal enzyme cathepsin D. Consistent with these results, treatment of cells with tunicamycin had no effect on autophagy-induced proteolysis. We conclude that lysosomal enzyme delivery to nascent AVs occurs primarily by the fusion of pre-existing mature lysosomes, with a much smaller contribution by MPRs or the PLC.
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PMID:Autophagic vacuoles rapidly fuse with pre-existing lysosomes in cultured hepatocytes. 132 48

Changes in the activity of proteases (cathepsin D and calpains) caused by 48-h food withdrawal were studied in the brain, liver, kidney, spleen, and heart of 3-, 12-, and 24-month-old Fischer rats. Cathepsin D activity was similar in brain, liver, and heart of control animals; in kidney it was 5-fold higher and in spleen about 10-fold higher. With age, activity increased in all organs tested except spleen. Brief starvation caused no change of cathepsin D activity in brain, but caused an increase in liver and a decrease in spleen. Neutral proteolytic activity in control was highest in the pons-medulla-cerebellum fraction of brain, and activity in liver and heart was below that in brain. Activity increased with age in brain and decreased in other organs. Brief starvation in young animals caused an increase in activity in brain, and a decrease in liver and spleen. Isolated calpain II activity was high in control brain. It increased with age in the cerebrum. Brief starvation resulted in a decrease in the brain. The results indicate that the protease content of the brain is altered with age and in malnutrition, with changes not being the same for all proteases, and changes in brain being different from those in other organs.
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PMID:Effects of brief starvation on brain protease activity. 178 26

Acute starvation of the wild-type of the nematode Caenorhabditis elegans depresses the level of cathepsin D by 65% within 4-8 h and the level of the thiol cathepsins Ce1 and Ce2 to about the same extent after 24 h. There is no parallel loss of lysosomal beta-glucosidase or beta-hexosaminidase activities. In strains which are chronically starved as a result of mutations which compromise feeding behaviour (unc-52) or nutrient uptake into the intestinal cells (daf-4), cathepsin D levels are decreased to about 15% of the level in fully fed wild-type animals. We suggest that the decline in the cathepsin D level results from autodigestion when alternative protein substrates are depleted in the lysosomes.
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PMID:Regulation of proteinase levels in the nematode Caenorhabditis elegans. Preferential depression by acute or chronic starvation. 251 5

Lysosomal enzyme activities in pancreatic islets of obese hyperglycemic ob/ob mice aged 3 to 6 months were investigated and compared with those of normal lean NMRI mice of the same age. It was observed that the glycogenolytic glucose-producing hydrolase acid amyloglucosidase displayed a fivefold higher activity in the islets of obese mice than in the islets of normal NMRI mice. However, other islet lysosomal enzyme activities measured, such as N-acetyl-beta-D-glucosaminidase and beta-glucuronidase, were of the same magnitude in both obese and lean mice. A starvation period of 24 hours induced a significant depression of islet acid amyloglucosidase activity in obese as well as lean mice, whereas the activities of N-acetyl-beta-D-glucosaminidase and beta-glucuronidase were unaffected. Further, the activities of other types of islet lysosomal enzymes, such as acid phosphatase and cathepsin D, were also measured in obese mice. These activities were not found to be affected by the actual fasting period. A good correlation (r = 0.815; P less than 0.01) was observed between islet acid amyloglucosidase activity and plasma insulin concentrations in obese mice, whereas no such relationship was apparent with regard to other islet lysosomal enzyme activities recorded. Acid amyloglucosidase activity in liver tissue of the obese mouse was about 30 times lower than that of islet tissue. Further, the activity of liver amyloglucosidase was of the same order of magnitude in obese and lean mice. Similarly, other lysosomal enzyme activities in the liver of obese and lean mice were not strikingly different.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lysosomal enzyme activities in pancreatic islets from normal and obese hyperglycemic mice. 391 27

Postnuclear supernates from homogenates of skeletal muscle from rats subjected to starvation, injections of Triton WR-1339, dextran-500, and dextran + corticosterone were fractionated by means of rate and isopycnic zonal centrifugation in sucrose-0.02 M KCl gradients. Zonal fractions were analyzed for protein, RNA, cytochrome oxidase, and up to six acid hydrolases. The results indicate the presence of two groups of lysosome-like particles. One group contributes approximately 95% of the cathepsin D and acid phosphatase activity and 75% of the acid ribonuclease, beta-glucuronidase, and arylsulfatase activity in muscle. It is characterized by a modal equilibrium density of 1.18 that is decreased by starvation, but is not shifted by dextran-500 or Triton WR-1339. The second group has a higher proportion of acid ribonuclease, beta-glucuronidase, and arylsulftase; the equilibrium density can be shifted by dextran-500 and Triton WR-1339. It is suggested that this group of lysosomes is derived from macrophages and other connective tissue cells, whereas the former group represents lysosome-like particles from muscle cells.
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PMID:Lysosomes in skeletal muscle tissue. Zonal centrifugation evidence for multiple cellular sources. 432 73

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. These responses are different from simultaneous changes in cardiac cathepsin D activity in several instances (starvation, corticosteroid treatment, aging and thyrotoxicosis). In the past, measurements of cathepsin D activity in heart have sometimes been considered to be representative of lysosomal proteinase activity in general and used as an index of cardiac lysosomal proteolytic capacity. The present results suggest that changes in cathepsin D do not necessarily reflect alterations in other lysosomal proteinases and may not serve as a valid indicator of overall lysosomal proteolytic capacity under all conditions.
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PMID:Changes in cardiac cathepsin B activity in response to interventions that alter heart size or protein metabolism: comparison with cathepsin D. 623 80

Starvation is characterized by rapid loss in liver weight and proteins. The loss in liver protein is reflected in loss of protein in most organelles including mitochondria, microsomes, and cytosol, with the exception of nuclei. The nuclear proteins increase per unit weight of liver during starvation and this holds true for both histone and non-histone fractions. Comparison of degradation pattern of histone and non-histone fractions with microsomal fraction indicates a significantly different profile. The nuclear proteins reflect a pattern of decreased degradation during starvation. The increase in the activity of lysosomal enzyme cathepsin D measured during this period was indicative of general increase in catabolic processes. However, the nuclear protease activity decreased during this period, suggesting an organelle compartmentation of degradation process.
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PMID:Effect of starvation on degradation of rat liver nuclear proteins. 639 70


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