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

Subconfluent FRTL cells were examined in the electron microscope after the following treatments: i) continuous TSH stimulation; ii) starvation from TSH for 3 or 7 days; iii) seven days of TSH deprivation followed by two days of TSH stimulation. The organelle complement of cells grown in the presence of TSH appeared to be consistent with their secretory properties. Rough endoplasmic reticulum (RER), in the form of round vesicles, and Golgi apparatus, were quite prominent. Cells were not properly polarized. Their dorsal surface was covered with microvilli and occasional pseudopods. After TSH withdrawal the cells flattened on the dish, lost most of their plasma membrane specializations and reorganized actin stress fibers. RER shape was modified from round vesicles to flat cisternae which thereafter almost completely disappeared. The Golgi apparatus did not seem to be modified. Autophagic vacuoles became more prominent. All the modifications were fully reversed after TSH replacement indicating an hormonal regulation in the amount and morphology of some organelle, in particular of the RER.
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PMID:Morphological changes induced by prolonged TSH stimulation or starvation in the rat thyroid cell line FRTL. 221 Jun 30

In this article we summarize our findings concerning a pathway by which cytosolic proteins can be selectively taken up and degraded within lysosomes. Serum deprivation of cells in culture activates this pathway, and only proteins that contain peptide sequences related to KFERQ are degraded at an enhanced rate. Approximately 30% of intracellular proteins contain such peptide sequences, and we speculate about the physiological relevance of the selective degradation of these proteins in response to serum withdrawal. Several rat tissues also contain proteins with peptide sequences related to KFERQ, and the amount of these proteins is reduced in response to starvation. Finally, we present recent results suggesting that this selective uptake of cytosolic proteins by lysosomes is not through classical macroautophagy. Instead, the selective uptake appears to be similar to other protein sorting pathways such as protein translocation through the endoplasmic reticulum or protein import into mitochondria.
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PMID:Peptide signals for protein degradation within lysosomes. 261 68

The degradation of intracellular protein and other cytoplasmic macromolecules in liver is an ongoing process that regulates cytoplasmic mass and provides amino acids for energy and other metabolic uses early in starvation. Cellular proteins are conveniently divided into two general classes according to readily discernable differences in average rates of turnover. A short-lived class, having a half-life of approximately 10 min, comprises about 0.6% of total protein. Its degradation is not physiologically controlled, and the mechanism is probably nonlysosomal in nature. The second or long-lived group, with an average half-life 250 times greater, constitutes more than 99% of the cell's protein. By contrast, its breakdown is strongly regulated, and the site of catabolism is believed to be the vacuolar-lysosomal system. Cytoplasmic sequestration by lysosomes can be divided into two categories; macro- and microautophagy. The first is induced by amino acid and/or insulin deprivation. Amino acids are considered to be primary regulators, since they can control this process over the full range of induced proteolysis in the absence of hormones. Glucagon, cyclic AMP, and beta-agonists also stimulate macroautophagy in hepatocytes but have opposite effects in myocytes. Micrautophagy differs from the former in that the cytoplasmic "bite" is smaller and the uptake process is not acutely regulated. However, the latter does decrease during starvation in parallel with basal proteolysis, effects that might be linked to the loss of endoplasmic reticulum. The primary control of macroautophagy is accomplished through a small group of direct regulators (Leu, Tyr/Phe, Gln, Pro, Met, His, and Trp) and a specific coregulatory action of alanine. As a group, regulatory amino acids produce direct inhibitory responses in the perfused rat liver that are identical to those of the complete amino acid mixture at 0.5x and 4x (times) normal plasma concentrations. However, they lose effectiveness almost completely within a narrow zone centered at normal levels, a loss that can be abolished by the addition of alanine at its normal plasma concentration (0.5 mM). At this level, alanine does not inhibit directly. Interestingly, this zonal loss is also eliminated by insulin. Glucagon, though, specifically blocks the initial inhibition evoked by 0.5x amino acid mixtures and thus induces maximal rates of protein degradation at normal amino acid concentrations.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Mechanism and regulation of protein degradation in liver. 264 36

In this article we summarize evidence for a pathway by which cytosolic proteins can be selectively taken up and degraded within lysosomes. Serum deprivation of cells in culture activates this pathway, and only proteins that contain peptide sequences related to KFERQ (lysine, phenylalanine, glutamic acid, arginine, glutamine) are degraded at enhanced rates. Approximately 30% of intracellular proteins contain such peptide sequences, and we speculate about the physiological relevance of the selective degradation of these proteins in response to serum withdrawal. Several rat tissues also contain proteins with peptide sequences related to KFERQ, and the amount of these proteins is reduced in response to starvation. Finally, we present recent results suggesting that this selective uptake of cytosolic proteins by lysosomes is not through classical macroautophagic pathways. Instead, the selective uptake may be similar to other protein sorting pathways such as protein translocation through the endoplasmic reticulum or protein import into mitochondria.
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PMID:Lysosomal degradation of microinjected proteins. 270 96

The ultrastructure of annulate lamellae in the pancreatic exocrine cells of rats starved for 3-42 days was studied. Annulate lamellae were rarely encountered in the pancreatic exocrine cells of control rats, but their incidence and size of stack was increased in those of starved rats depending on the duration of starvation, despite marked ultrastructural changes in these cells. Annulate lamellae were located in the para- or infranuclear cytoplasm of the cells and most of them were continuous with the relative normal rough endoplasmic reticulum. A close apposition in parallel was often found between the annulate lamellae and the outer nuclear envelope and occasionally pores in line with those of the nuclear membrane were observed in the lamellae of rough endoplasmic reticulum in 35- and 42-day-starved rats. An unequivocal continuity between the annulate lamellae and the nucleus and/or rough endoplasmic reticulum in pancreatic exocrine cells might be related to their origin and function.
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PMID:Annulate lamellae of the pancreatic exocrine cells in starved rats. 287 54

Ultrastructural changes of the pancreatic exocrine cells after 3, 7, 14, 21, 28, 35 and 42 days of starvation were observed in male rats aged from 16 to 18 months weighing between 600 and 700 grams. The number of zymogen granules after starvation decreased to less than about 70 per cent of that of the control. Changes in the rough endoplasmic reticulum were hardly seen up to 14 days of starvation as compared with the control, but were observed in the apical and basal cytoplasm of the cell from 21 days after starvation. Particularly in 35- and 42-day starved rats, the rough endoplasmic reticulum was frequently shortened and dilated, and changed to disorganized membranous structures. The lysosomes in the apical cytoplasm of the cell gradually increased in number after starvation, and contact or fusion between the zymogen granules and lysosomes (viz, so-called crinophagy) was often seen at 35 and 42 days of starvation. Large autolysosomes especially those containing zymogen granules and rough endoplasmic reticulum were also marked in the basal cytoplasm of the cell after 35 and 42 days of starvation. Alterations in the basal cytoplasm of the cell appeared later than those in the apical cytoplasm. It was considered that, owing to its role in protein synthesis, the basal cytoplasm of the pancreatic exocrine cells in starved rats might be protected as far as possible during long-term starvation.
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PMID:Ultrastructure of pancreatic exocrine cells of the rat during starvation. 298 Jan 1

We have characterized a cDNA clone that encodes a protein related to the 70 kd heat shock protein, but is expressed in normal rat liver. This protein has a hydrophobic leader and is secreted into the endoplasmic reticulum. We show that it is identical with two previously described proteins: GRP78, whose synthesis is induced by glucose starvation, and BiP, which is found bound to immunoglobulin heavy chains in pre-B cells. This protein, which is abundant in antibody-secreting cells, can be released from heavy chains by ATP, a reaction analogous to the release of hsp70 from heat shocked nuclear structures. We propose a specific role for this protein in the assembly of secreted and membrane-bound proteins.
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PMID:An Hsp70-like protein in the ER: identity with the 78 kd glucose-regulated protein and immunoglobulin heavy chain binding protein. 308 29

The 78,000-dalton glucose-regulated protein (GRP78) and the immunoglobulin heavy-chain-binding protein (BiP) were shown to be the same protein by NH2-terminal sequence comparison. Immunoprecipitation of GRP78-BiP induced by glucose starvation and a temperature-sensitive mutation in a hamster fibroblast cell line demonstrated the association of GRP78-BiP with other cellular proteins. In both fibroblasts and lymphoid cells, GRP78-BiP was found to label with 32Pi and [3H]adenosine. Phosphoamino acid analysis demonstrated that GRP78-BiP is phosphorylated on serine and threonine residues. Conditions which induce increased production of GRP78-BiP resulted in decreased incorporation of 32Pi and [3H]adenosine into GRP78-BiP. Furthermore, we report here that the phosphorylated form of BiP resides in the endoplasmic reticulum and that BiP which is associated with heavy chains is not phosphorylated or labeled with [3H]adenosine, whereas free BiP is. This suggests that posttranslational modifications may be important in regulating the synthesis and binding of BiP.
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PMID:Identity of the immunoglobulin heavy-chain-binding protein with the 78,000-dalton glucose-regulated protein and the role of posttranslational modifications in its binding function. 314 86

Short-term (24 h) starvation induced a significant decrease in the liver weight and in the average volume of hepatocytes, together with a notable decrease in the hepatic concentration of proteins, glycogen, cholesterol and triglycerides. Hepatocyte atrophy was due for about 95% to the decrease in the membrane space, in which glycogen and endoplasmic reticulum membranes are contained, and for about 5% to the depletion of lipid droplets, in which cholesterol and triglycerides are stored. Nuclei, mitochondria and rough endoplasmic reticulum did not display appreciable modifications. The smooth endoplasmic reticulum underwent a net decrease, comparable with the decrease in the liver protein content, and the volume of dense-body compartment was increased, mainly through the rise in the number of microautophagic vacuoles and secondary lysosomes. These last findings were interpreted as the morphological counterpart of the fasting-induced enhancement of protein degradation in rat liver.
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PMID:A morphometric study of the effects of short-term starvation on rat hepatocytes. 322 40

The continuous turnover of intracellular protein and other macromolecules is a basic cellular process that serves, among other functions, to regulate cytoplasmic content and provide amino acids for ongoing oxidative and biosynthetic reactions during nutrient deprivation. The intensity of breakdown and pattern of regulation, though, vary widely among cells. Rat hepatocytes, for example, exhibit high absolute rates of proteolysis and regulatory effects that diminish during starvation, while corresponding responses in skeletal and cardiac muscle move in the opposite direction. It is also becoming apparent that effects of insulin and other acute regulatory agents on muscle breakdown are limited to nonmyofibrillar components. The latter may be sequestered and degraded within autophagic vacuoles, whereas myofibrillar proteins require an initial attack by calcium-dependent proteases in the cytosol. By contrast, most if not all of the breakdown of resident (long-lived) proteins as well as RNA in the hepatocyte can be explained by lysosomal mechanisms. The uptake of cytoplasmic components by lysosomes can be divided into two major categories, macroautophagy and micro- or basal autophagy. The first is induced by amino acid or insulin/serum deprivation. In the hepatocyte, amino acids alone can regulate this process almost instantaneously over two thirds of the full range of proteolysis, 4.5% to 1.5% per hour. Glucagon, cyclic AMP, and beta-agonists also stimulate macroautophagy in hepatocytes but have opposite effects in skeletal and cardiac myocytes. Basal autophagy differs from the macro type in that the cytoplasmic "bite" is smaller and sequestration is not acutely regulated. It is, however, adaptively decreased during starvation in parallel with absolute rates of basal turnover. Since endoplasmic reticulum comprises an appreciable fraction of the vacuolar content, volume sequestration would be compatible with the known heterogeneity of individual protein turnover if some proteins (or altered proteins) selectively bind to membranes. The amino acid control of macroautophagy in the hepatocyte is accomplished by a small group of direct inhibitors (Leu, Tyr/Phe, Gln, Pro, Met, Trp, and His) and the permissive effect of alanine whereas only leucine is involved in myocytes and adipocytes. Of unusual interest is the fact that the inhibitory amino acid group alone evokes responses in perfused livers that are identical to those of a complete plasma mixture at 0.5 and 4 times normal plasma levels but loses effectiveness almost completely at normal concentrations.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Intracellular protein catabolism and its control during nutrient deprivation and supply. 330 Jul 46


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