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)

Gluconeogenesis, the de novo formation of glucose from non-carbohydrate precursors, is confined to the proximal convoluted and proximal straight tubules of the mammalian kidney. Compared to liver, renal gluconeogenesis has different substrate requirements and responds to different regulatory stimuli. Stimuli in kidney include starvation, metabolic acidosis, glucocorticoid treatment, and, possibly, PTH and catecholamines. Regulation of gluconeogenic flux occurs at three or four key enzyme sites, particularly phosphoenolpyruvate carboxykinase (PEPCK) and fructose 1,6-bisphosphatase. Interest has focused on the relation among H+, Ca2+, and cyclic AMP in the hormonal regulation of gluconeogenesis. The importance of other putative regulators including fructose 2,6-bisphosphate remains to be determined.
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PMID:Renal gluconeogenesis. 306 2

Palmitate ability to modify D-[U-14C]glucose incorporation into different lipids ("de novo" synthesis), as well as sugar-stimulation of insulin release and 45Ca2+-fluxes, was investigated in islets of fed and 48-h starved rats. The fatty-acid induced dose-dependent, correlative increments of insulin secretion, 45Ca2+-influx and the "de novo" synthesis of each phospholipid fraction analysed at 20 mmol/l (but not 3 mmol/l) glucose. Omission of calcium reduced drastically (p less than 0.001) insulin release and the "de novo" synthesis of neutral glycerolipids, leaving unaltered that of acidic phospholipids (phosphatidate and phosphoinositides). The increased synthesis of the latter is therefore not the consequence of stimulated secretion. It could initiate or contribute to maintain an increased turnover of islet phosphoinositides, thus generating some mediators of the calcium signalling system (inositol phosphates). Starvation led to a drastic reduction (p less than 0.001) of both insulin secretion, "de novo" synthesis of each lipid fraction, and 45Ca2+-influx in response to glucose and palmitate. The presence of a fatty-acid oxidation inhibitor (2-bromostearate or 2-tetradecylglycidate) prevented the effect of starvation on 45Ca2+-influx, as it has been shown to do on insulin secretion and palmitate incorporation into islet lipids. It is finally suggested that palmitate might amplify the insulin secretory response of islets to glucose, through the stimulation of the "de novo" synthesis of phosphoinositides and the subsequent generation of inositol phosphates, which would contribute to accelerated calcium turnover.
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PMID:Palmitate dependence of insulin secretion, "de novo" phospholipid synthesis and 45Ca2+-turnover in glucose stimulated rat islets. 306 35

Treatment of the rat pancreatic acinar cell line AR4-2J with the calcium ionophore A23187 selectively increases, within a few hours, the steady-state level of trypsin mRNA. Addition of the tumor-promoting phorbol ester phorbol 12-myristate 13-acetate potentiates the calcium-induced increase. The mRNA level of the other tested exocrine pancreatic genes decreases. These results were confirmed by DNA transfection experiments, using the 5' flanking region of the trypsin and chymotrypsin genes linked to the coding sequence of the chloramphenicol acetyltransferase (CAT) gene. In calcium-induced cells transfected with the trypsin constructs, an increase in CAT activity was observed, whereas the chymotrypsin constructs revealed a decreased CAT activity. Glucose starvation of AR4-2J cells similarly elicited a selective increase in trypsin mRNA. This selective regulation of trypsin may reflect its role as the key activator of the other zymogen species.
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PMID:Selective regulation of trypsin gene expression by calcium and by glucose starvation in a rat exocrine pancreas cell line. 308 79

Animal cells respond to calcium ionophore (A23187) treatment with the coordinate induction of a set of genes encoding proteins identical to the glucose-regulated proteins (GRPs). By monitoring the intracellular free calcium with the fluorescent indicator fura-2 while employing both intracellular and extracellular calcium buffers, we demonstrated that A23187 can induce the GRP94 and GRP78 genes without an increase in cytoplasmic calcium ([Ca2+]i). Induction of GRP mRNA during glucose starvation was also independent of [Ca2+]i. Instead, gene induction by A23187 was closely correlated with the depletion of intracellular calcium stores. We conclude that perturbations of sequestered calcium ions by A23187 can serve as a stimulus for gene expression.
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PMID:Depletion of intracellular calcium stores by calcium ionophore A23187 induces the genes for glucose-regulated proteins in hamster fibroblasts. 311 64

The nickel transport system of Clostridium thermoaceticum was investigated with 63NiCl2 and an anaerobic microfiltration transport assay. Transport was optimal at pH 7 to pH 7.5 and 65 degrees C and decreased in the presence of metabolic uncouplers and inhibitors. Exogenous nickel was concentrated 3,000-fold over the apparent nickel concentration gradient during typical transport assays. Stored cellular energy appeared to provide a short-term energy source to power nickel transport, and starvation experiments demonstrated external energy source stimulation of nickel translocation. The apparent Km and Vmax for nickel transport by carbon monoxide-dependent chemolithotrophic cells approximated 3.2 microM Ni and 400 pmol of Ni transported per min per mg of cells (dry weight), respectively. Magnesium, calcium, cobalt, iron, manganese, and zinc did not inhibit the transport of nickel.
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PMID:Energy-dependent, high-affinity transport of nickel by the acetogen Clostridium thermoaceticum. 319 12

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

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 role of the IFN-induced enzyme 2' - 5' oligo (A) synthetase in the regulation of cell growth was analyzed by transfecting its reaction product into cells in the G1 and S phases of the cell cycle. Using the calcium phosphate transfection method, we found that the oligonucleotide was very stable compared to the levels reported to be induced by IFN. Under these circumstances, exponentially growing cells were blocked in the S phase as expected from previous results from studies on IFN treatment. In contrast, cells synchronized by serum starvation and readdition of serum were blocked in the cell cycle phase, where they resided when transfected. Precipitated oligonucleotide had drastic effects with degradation of rRNA and c-myc mRNA, in contrast to IFN-treated cultures where such effects were not detectable. 2' - 5' oligo (A) synthetase activity started to increase 6 hours after restimulation of quiescent cells with IFN and serum. We propose that several molecular targets may exist for the 2' - 5' oligo (A) system, and that the kinetics of expression of the oligonucleotide after addition of IFN determine the type of cell cycle block obtained in different tumor cells in vivo.
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PMID:Interferon-induced inhibition of a malignant glioma cell line. Possible role of the 2' - 5' oligo (A) system. 338 34

A gelsolin-like actin-modulating protein was isolated from rat skeletal muscle and characterized with respect to its interaction with actin. The protein, with a molecular mass of approx. 85 kDa, forms a stoichiometric complex with two actin molecules and is activated by micromolar concentrations of Ca2+. It effectively severs actin filaments and promotes nucleation of actin polymerization. The activity of this protein is detectable already in crude extracts by its capability to reduce the steady state viscosity of actin. Actin-modulating activities were determined in muscle extracts of rats kept under protein catabolic conditions, i.e. as generated by corticosterone treatment and starvation. In both cases we found a marked increase of modulator activity. The possibility is discussed that the increased activity of actin modulator indicates a fragmentation of actin filaments prior to the proteolytic degradation of actin.
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PMID:Activity of a gelsolin-like actin modulator in rat skeletal muscle under protein catabolic conditions. 343 53

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


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