Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two glucose-regulated proteins, GRP78 and GRP94, are major constituents of the endoplasmic reticulum (ER) of mammalian cells. These proteins are synthesized constitutively in detectable amounts under normal growth conditions; they can also be induced under a variety of conditions of stress including glucose starvation and treatment with drugs that inhibit cellular glycosylation, with calcium ionophores or with amino-acid analogues. Unlike the closely-related heat shock protein (HSP) family, the GRPs are not induced significantly by high temperature. Recently, GRP78 has been identified as the immunoglobulin heavy chain binding protein (BiP) (ref. 5 and Y.K. et al., in preparation) which binds transiently to a variety of nascent, wild-type secretory and transmembrane proteins and permanently to malfolded proteins that accumulate within the ER. We have tested the hypothesis that the presence of malfolded proteins may be the primary signal for induction of GRPs by expressing wild-type and mutant forms of influenza virus haemagglutinin (HA) in simian cells. Only malfolded HAs, whose transport from the ER is blocked, induced the synthesis of GRPs 78 and 94. Additional evidence is presented that malfolding per se, rather than abnormal glycosylation, is the proximal inducer of this family of stress proteins.
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PMID:The presence of malfolded proteins in the endoplasmic reticulum signals the induction of glucose-regulated proteins. 335 47

The immunocytochemical localization of fatty acid binding protein (FABP) of liver type was studied at light and electron microscopic levels by the peroxidase-antiperoxidase (PAP) method using a specific polyclonal antibody against FABP in the liver of fed and fasted rats. In the liver of rats fed ad libitum, the intense immunoreactivity was confined to portions of the liver cell cytoplasm adjacent to the glycogen area. After 2-days' fasting, such a focal intracellular localization of the immunoreactivity was abolished, in association with the disappearance of the glycogen area, and was replaced by a diffuse distribution of the immunoreactivity throughout the cytoplasm, with higher intensity at the periphery of the cells. In liver cells exhibiting an overall hypertrophy of smooth endoplasmic reticulum (SER) induced by the treatment of fasted rats with phenobarbital, the peripheral localization of FABP immunoreactivity remained unchanged compared with that obtained in the case of fasting alone, and the immunoreactivity did not occur in association with the proliferated SER in the central cytoplasm. These results suggest that FABP, although cytosolic in nature, changes its localization within the liver cells in response to the general metabolic alterations caused by the starvation, inferring that FABP is intimately involved in the intracellular transport and metabolism of free fatty acids.
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PMID:Immunocytochemical localization of hepatic fatty acid binding protein in the liver of fed and fasted rats. 341 Jul 44

The 78-kDa glucose-regulated protein GRP78 is a stress-inducible protein ubiquitously expressed in animal cells. In this paper we show that the first exon of this endoplasmic reticulum-localized protein consists of an 18 amino acid leader sequence rich in hydrophobic residues, followed by a highly acidic mature N-terminus and an 11 amino acid domain that is shared by members of the 70-kDa heat shock protein family. The end of this shared domain also marks the beginning of the first intron of this gene. A DNA region upstream of the promoter element important for induction by calcium ionophore and by a temperature-sensitive mutation was identified by deletion analysis. Our results indicate that a region spanning from 85 to 480 nucleotides upstream of the major transcription initiation site is important for both induction conditions. With evidence suggesting that perturbations in protein glycosylation may be one of the common stimuli involved in transcription activation of the GRPs, we measured the rate of glycosylation during A23187, glucose starvation, and temperature-shift induced conditions. The inverse correlation observed between the rate of glycosylation and the steady-state level of the GRP78 transcripts lends support to this hypothesis.
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PMID:Rat gene encoding the 78-kDa glucose-regulated protein GRP78: its regulatory sequences and the effect of protein glycosylation on its expression. 346 6

The bulk of cellular protein in hepatocytes is sequestered and degraded by two classes of autophagy, (a) an overt or macro form, and (b) microautophagy. Macroautophagy is rapidly induced by amino acid deprivation and the administration of glucagon and suppressed by amino acids and insulin. Amino acids appear to be its primary regulator since liver perfusion studies have shown that it can be inhibited almost completely and proteolysis decreased from maximal (4.5% hr) to basal rates (1.7%/hr) by 4 times normal plasma amino acid concentrations. The resulting alterations in the aggregate volume of autophagic vacuoles are associated with proportional changes in the amount of cytoplasmic protein sequestered and in rates of protein degradation. Since the apparent turnover of autophagic vacuoles is 0.087 min-1, the pools of sequestered protein at all levels of macroautophagic stimulation are sufficient to account fully for the observed rates of accelerated rate of proteolysis. Microautophagy differs from the former in that the cytoplasmic 'bite' is smaller and it is not subject to acute physiological regulation. It is, however, dramatically decreased to near zero during refeeding after prior starvation. These and other findings indicate that it is adaptively regulated, possibly as a consequence of alterations in the amount of smooth endoplasmic reticulum. The amino acid control of accelerated protein degradation appears to involve direct inhibition by a small group of amino acids (Leu, Tyr/Phe, Gln, Pro, Met, Trp, and His) and the permissive action of alanine. Of unusual interest is the fact that, whereas the inhibitory amino acid group evokes responses identical to a complete amino acid mixture at 0.5x and 4x normal amino acid concentrations, it loses its effectiveness at normal levels; similar responses have been shown for leucine alone. The loss of effectiveness at normal concentrations is abolished by the addition of 0.5 mM alanine which by itself is not directly inhibitory. No other amino acid can replace alanine. These findings suggest a novel role for alanine that could be of importance in linking energy demands to proteolysis. A hypothetical model for proteolytic regulation by leucine and the other inhibitory amino acids is presented.
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PMID:The lysosomal pathway of intracellular proteolysis in liver: regulation by amino acids. 349 68

The ultrastructure of annulate lamellae of the jejunal absorptive cells in control and 21 d starved rats was investigated. Annulate lamellae were only rarely encountered in the jejunal absorptive cells of control rats, and then frequently in small stacks continuous with the rough-surfaced endoplasmic reticulum. In contrast, there was a relatively frequent incidence of annulate lamellae in the jejunal absorptive cells of 21 d starved rats, and larger stacks of annulate lamellae were also observed in spite of marked ultrastructural changes of these cells. The annulate lamellae were also continuous with the rough-surfaced endoplasmic reticulum, which was degenerating. The degenerative process of the absorptive cells following starvation might be related to the origin and function of the annulate lamellae.
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PMID:Annulate lamellae of the jejunal absorptive cells in 21-day-starved rats. 393 52

Ultrastructural changes of the parathyroid glands of starved mice were examined. The parathyroid glands of the starved mice showed a decrease in the volume of Golgi complexes and storage granules and an increase in the volume of lipid droplets, and contained more heterogeneously dense bodies and multivesicular bodies compared with that of the control mice. In addition, the volume of mitochondria, cisternae of granular endoplasmic reticulum and secretory granules and the number of prosecretory granules appeared to be decreased compared to those of the control mice. Myelin-like structures were observed in the parathyroid glands of the starved mice. The results of our study provide support for the hypothesis that starvation exerts an inhibitory influence not only on the synthesis but also on release of parathyroid hormone.
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PMID:Effects of starvation on the ultrastructure of the mouse parathyroid gland. 396 23

Morphometric and biochemical techniques were used to analyze hepatic glycogen, endoplasmic reticulum, and mitochondrial matrix granules in rats treated with compound 48/80 to induce an anaphylactic-like state of shock. Thirty minutes after insult there was a significant decrease in glycogen and mitochondrial matrix granules, an increase in rough endoplasmic reticulum (RER), and no change in smooth endoplasmic reticulum (SER). Less glycogen in experimental rats substantiated a previously described glycogenolytic response to compound 48/80. The decrease in matrix granules implies a loss and/or shift in intramitochondrial calcium as occurs in epinephrine-induced glycogenolysis in the rat. Since other glycogenolytic agents, e.g. glucagon, and starvation stimulate an increase in SER presumably from RER, the present morphological data suggest the increase in RER may precede proliferation of SER from RER.
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PMID:Morphometric analysis of hepatocytes from rats subjected to compound 48/80-induced anaphylactic shock. 401 63

CULTURED KB CELLS (DERIVED FROM A HUMAN ORAL CARCINOMA) GROWN IN MONOLAYERS WERE INJURED BY ONE OF THREE AGENTS: starvation by arginine deprivation or treatment with high doses of either ultraviolet radiation or x-radiation. The different agents produced changes in nucleolar structure and varying accumulations of triglyceride and glycogen. All three agents produced an increase in number and size of lysosomes. These were studied in acid phosphatase preparations, viewed by both light and electron microscopy, and, occasionally, in vital dye, esterase, and aryl sulfatase preparations. Ultrastructurally, alterations in lysosomes suggested that "residual bodies" developed in a variety of ways, i.e., from the endoplasmic reticulum, multivesicular bodies, or autophagic vacuoles. Following all three agents the endoplasmic reticulum assumed the form of "rough" or "smooth" whorls, and, after two of the agents, arginine deprivation or ultraviolet radiation, it acquired cytochemically demonstrable acid phosphatase activity. Near connections between the endoplasmic reticulum and lysosomes raise the possibility that in KB cells, at least when injured, the endoplasmic reticulum is involved in the formation of lysosomes and the transport of acid phosphatase to them.
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PMID:Effects of arginine deprivation, ultraviolet radiation, and x-radiation on cultured KB cells. A cytochemical and ultrastructural study. 532 75

1. A centrifugation method for the fractionation of the postmitochondrial fraction from rat-liver homogenates is described. The technique, in which no detergent is used, may be used as a tool to discriminate between two classes of ribosomes. One class is firmly bound to membranes and the other consists either of free polysomes or of ribosomes attached by weaker forces to the membranes of the endoplasmic reticulum. 2. Electron-micrograph studies revealed that the polysomes were not contaminated with bound ribosomes or with membranous fragments. 3. The separated fractions were characterized by their RNA, protein, ribonuclease and phospholipid content. 4. The influence of starvation on the RNA and protein contents of the different fractions was investigated. 5. Labelling of the various centrifugal fractions in vivo revealed no difference in uptake of radioactive amino acid between the two classes of ribosomes. 6. Incorporation of radioactive leucine in vitro and the polyuridylic acid-directed phenylalanine incorporation were similar for both classes of ribosomes.
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PMID:Isolation and properties of polyribosomes and fragments of the endoplasmic reticulum from rat liver. 603 56

The in vitro lipid requirements of UDP-N-acetylglucosamine-dolichol phosphate N-acetylglucosamine-1-phosphotransferase for the inositol-containing sphingolipids from Saccharomyces cerevisiae were characterized in terms of concentration and specificity. The effects of combinations of lipids, especially phosphatidylinositol and the inositol-containing sphingolipids, were also tested on the transferase. Phosphatidylinositol and phosphatidylglycerol stimulated the enzyme 3.3- and 2.8-fold, respectively. The inositol-containing sphingolipids, phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine did not stimulate the activity of the transferase. Phosphatidylcholine and phosphatidylethanolamine in combination with phosphatidylinositol had no effect on the transferase activity; however, the inositol-containing sphingolipids markedly inhibited the stimulation of the transferase by phosphatidylinositol. This inhibition by the sphingolipids was prevented if phosphatidylcholine, in addition to the other lipids, was present in the assay mixture. In addition, changes due to inositol starvation in the in vivo membrane lipid environment, i.e., phosphatidylinositol and the inositol-containing sphingolipids, were analyzed to determine whether they corresponded to the observed in vitro effects. Three hours after the beginning of inositol starvation, there were 9- and 14-fold reductions in the accumulation of phosphatidylinositol in membrane fractions IIA (vesicles) and IV (endoplasmic reticulum), respectively, although there was only a 6-fold reduction in membrane fraction I (plasma membrane). The accumulation of [14C]inositol into inositol-containing sphingolipids also reflected the differences in the cellular location of membranes.
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PMID:Role of inositol-containing sphingolipids in Saccharomyces cerevisiae during inositol starvation. 609 Mar 93


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