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

When Pseudomonas aeruginosa is grown with organosulfur compounds as sulfur sources, it synthesizes a set of proteins whose synthesis is repressed in the presence of sulfate, cysteine, or thiocyanate (so-called sulfate starvation-induced proteins). The gene encoding one of these proteins, PA13, was isolated from a cosmid library of P. aeruginosa PAO1 and sequenced. It encoded a 381-amino-acid protein that was related to several reduced flavin mononucleotide (FMNH2)-dependent monooxygenases, and it was the second in an operon of three genes, which we have named msuEDC. The MsuD protein catalyzed the desulfonation of alkanesulfonates, requiring oxygen and FMNH2 for the reaction, and showed highest activity with methanesulfonate. MsuE was an NADH-dependent flavin mononucleotide (FMN) reductase, which provided reduced FMN for the MsuD enzyme. Expression of the msu operon was analyzed with a transcriptional msuD::xylE fusion and was found to be repressed in the presence of sulfate, sulfite, sulfide, or cysteine and derepressed during growth with methionine or alkanesulfonates. Growth with methanesulfonate required an intact cysB gene, and the msu operon is therefore part of the cys regulon, since sulfite utilization was found to be CysB independent in this species. Measurements of msuD::xylE expression in cysN and cysI genetic backgrounds showed that sulfate, sulfite, and sulfide or cysteine play independent roles in negatively regulating msu expression, and sulfonate utilization therefore appears to be tightly regulated.
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PMID:A novel reduced flavin mononucleotide-dependent methanesulfonate sulfonatase encoded by the sulfur-regulated msu operon of Pseudomonas aeruginosa. 1004 77

When a buffered anaerobic cell suspension of Methanococcoides methylutens was maintained under methanol-limited conditions, intracellular glycogen and hexose phosphates were consumed rapidly and a very small amount of methane formed at 4 h of a starvation period. When methanol was supplemented after a total of 20 h of starvation, a reverse pattern was observed: the glycogen level and the hexose phosphate pool increased, and formation of methane took place after a lag period of 90 min. A considerable amount of methane was formed in 120 min after its detection with a rate of 0.18 micromol mg(-1) protein min(-1). When methane formation decreased after 270 min of incubation and finally came to a halt, probably due to complete assimilation of supplemented methanol, the levels of glycogen and hexose monophosphates decreased once again. However fructose 1,6-diphosphate levels showed a continuous increase even after exhaustion of methane formation. In contrast to the hexose phosphate pool, levels of other metabolites showed a small increase after addition of methanol. The enzyme profile of glycogen metabolism showed relatively high levels of triose phosphate isomerase. Glyceraldehyde 3-phosphate dehydrogenase reacted with NADPH with a three-fold higher activity as compared to that with NADH.
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PMID:Metabolite and enzyme profiles of glycogen metabolism in Methanococcoides methylutens. 1132 49

Cytosolic redox balance has to be maintained in order to allow an enduring cellular metabolism. In other words, NADH generated in the cytosol has to be re-oxidized back to NAD(+). Aerobically this can be done by respiratory oxidation of cytosolic NADH. However, NADH is unable to cross the mitochondrial inner membrane and mechanisms are required for conveying cytosolic NADH to the mitochondrial electron transport chain. At least two such systems have proved to be functional in S. cerevisiae, the external NADH dehydrogenase (Luttik et al., 1998; Small and McAlister-Henn, 1998) and the G3P shuttle (Larsson et al., 1998). The aim of this investigation was to study the regulation and performance of these two systems in a wild-type strain of S. cerevisiae using aerobic glucose- and nitrogen-limited chemostat cultures. The rate of cytosolic NADH formation was calculated and as expected there was a continuous increase with increasing dilution rate. However, measurements of enzyme activities and respiratory activity on isolated mitochondria revealed a diminishing capacity at elevated dilution rates for both the external NADH dehydrogenase and the G3P shuttle. This suggests that adjustment of in vivo activities of these systems to proper levels is not achieved by changes in amount of protein but rather by, for example, activation/inhibition of existing enzymes. Adenine nucleotides are well-known allosteric regulators and both the external NADH and the G3P shuttle were sensitive to inhibition by ATP. The most severe inhibition was probably on the G3P shuttle, since one of its member proteins, Gpdp, turned out to be exceptionally sensitive to ATP. The external NADH dehydrogenase is suggested as the main system employed for oxidation of cytosolic NADH. The G3P shuttle is proposed to be of some importance at low growth rates and perhaps its real significance is only expressed during starvation conditions.
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PMID:Cytosolic redox metabolism in aerobic chemostat cultures of Saccharomyces cerevisiae. 1132 72

The mammalian pyruvate dehydrogenase complex (PDC) plays central and strategic roles in the control of the use of glucose-linked substrates as sources of oxidative energy or as precursors in the biosynthesis of fatty acids. The activity of this mitochondrial complex is regulated by the continuous operation of competing pyruvate dehydrogenase kinase (PDK) and pyruvate dehydrogenase phosphatase (PDP) reactions. The resulting interconversion cycle determines the fraction of active (nonphosphorylated) pyruvate dehydrogenase (E1) component. Tissue-specific and metabolic state-specific control is achieved by the selective expression and distinct regulatory properties of at least four PDK isozymes and two PDP isozymes. The PDK isoforms are members of a family of serine kinases that are not structurally related to cytoplasmic Ser/Thr/Tyr kinases. The catalytic subunits of the PDP isoforms are Mg2+-dependent members of the phosphatase 2C family that has binuclear metal-binding sites within the active site. The dihydrolipoyl acetyltransferase (E2) and the dihydrolipoyl dehydrogenase-binding protein (E3BP) are multidomain proteins that form the oligomeric core of the complex. One or more of their three lipoyl domains (two in E2) selectively bind each PDK and PDP1. These adaptive interactions predominantly influence the catalytic efficiencies and effector control of these regulatory enzymes. When fatty acids are the preferred source of acetyl-CoA and NADH, feedback inactivation of PDC is accomplished by the activity of certain kinase isoforms being stimulated upon preferentially binding a lipoyl domain containing a reductively acetylated lipoyl group. PDC activity is increased in Ca2+-sensitive tissues by elevating PDP1 activity via the Ca2+-dependent binding of PDP1 to a lipoyl domain of E2. During starvation, the irrecoverable loss of glucose carbons is restricted by minimizing PDC activity due to high kinase activity that results from the overexpression of specific kinase isoforms. Overexpression of the same PDK isoforms deleteriously hinders glucose consumption in unregulated diabetes.
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PMID:Distinct regulatory properties of pyruvate dehydrogenase kinase and phosphatase isoforms. 1164 66

In the present paper we show that transendothelial migration of a subset of CD14(+) circulating leukocytes, coexpressing the CD34 precursor marker, leads to protection from the apoptosis that follows growth factor(s) withdrawal. The resistance of this cell subset to starvation-induced programmed cell death, lasting from 48 to 96 hours, is accompanied by a rise of mitochondrial adenosine triphosphate (ATP), a high nicotinamide adenine dinucleotide (NAD)/reduced nicotinamide adenine dinucleotide (NADH) ratio, and by the up-regulation of expression of the antiapoptotic proteins Bcl-2 and Bcl-X, together with an increase in the cytoplasmic, inactive, form of Bax. This suggests that protection from apoptosis is due to the preservation of mitochondrial function(s). Interestingly, ligation of the platelet endothelial cell adhesion molecule-1 (PECAM-1), which drives CD14(+)CD34(+) transendothelial migration, leads to an increase in Bcl-2 A1 and Bcl-X intracellular content, and to protection from starvation-induced apoptosis. This event is dependent on the engagement of phosphatidylinositol-3 kinase and activation of Akt/PKB that is known to contribute to Bcl-2 and Bcl-X induction. These data point to a critical role of endothelium in preventing the apoptotic program triggered by starvation, possibly inducing a prolonged survival of antigen presenting cell precursors, in order to allow recirculation of these cells and localization to the site of priming of T lymphocytes.
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PMID:Transendothelial migration leads to protection from starvation-induced apoptosis in CD34+CD14+ circulating precursors: evidence for PECAM-1 involvement through Akt/PKB activation. 1239 47

An arbitrary-primed RNA PCR differential display strategy was used to identify midgut genes of the reduviid bug Triatoma infestans that were differentially expressed after a blood meal. From interesting bands, 33 distinct cDNAs were cloned and sequenced. Although many had long open reading frames, most of the transcripts were unrelated to any other sequences in any databases. Only 14 Triatoma sequences had strong homologies to those from other organisms, including genes encoding for 2-oxoglutarate dehydrogenase, CAD protein, NADH-ubiquinone-oxoreductase, epidermal growth factor, plectin, aminopeptidase, heat-shock-related 70-kDa protein, golgin, mitochondrial carrier protein and high-density lipoprotein. RT-PCR was used to demonstrate constitutive expression in four of five of these sequences. Northern hybridisation was difficult due to the very low expression levels of most of the genes. However, a gene-fragment highly homologous to a heat-shock-related 70-kDa protein was strongly expressed in starved bugs, down-regulated after feeding and again expressed later, suggesting a role for a heat-shock protein in starvation survival.
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PMID:Differential display of mRNAs associated with blood feeding in the midgut of the bloodsucking bug, Triatoma infestans. 1244 50

Survival, electron transport system (ETS) activity and the activity of NADH and succinate dehydrogenase of Escherichia coli ML30 were studied under starvation stress at different temperatures in a filtered-autoclaved lake water microcosm. ETS activity in E. coli declined rapidly at 30 degrees C but more slowly at 4 degrees and 15 degrees C over a 20 d starvation period. The decrease in ETS activity in E. coli only started after 6 d of incubation at 4 degrees C and 15 degrees C. Viability of E. coli, as determined by plate counts, declined faster at 37 degrees C than at the other temperatures and remained highest at 4 degrees C in filtered-autoclaved lake water. There was also a significant cell size reduction at 37 degrees C in filtered-autoclaved lake water but not at 4 degrees C. ETS activity after up to 16 d of starvation increased after the addition of nutrient broth to the filtered-autoclaved lake water at 15 degrees C and 30 degrees C suggesting that cells were still able to respond to nutrients, even after prolonged starvation. The response to the addition of nutrient broth, however, declined with the length of the starvation period. The activity of both succinate and NADH dehydrogenase declined over a 13 d starvation period. The loss of activity was fastest at 37 degrees C compared to lower incubation temperatures but even at 4 degrees C, a significant proportion of the activity was lost over the 13 d period.
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PMID:Relationship between respiratory enzymes and survival of Escherichia coli under starvation stress in lake water. 1245 93

Altered pyruvate dehydrogenase (PDH) functioning occurs in primary PDH deficiencies and in diabetes, starvation, sepsis, and possibly Alzheimer's disease. Currently, the activity of the enzyme complex is difficult to measure in a rapid high-throughput format. Here we describe the use of a monoclonal antibody raised against the E2 subunit to immunocapture the intact PDH complex still active when bound to 96-well plates. Enzyme turnover was measured by following NADH production spectrophotometrically or by a fluorescence assay on mitochondrial protein preparations in the range of 0.4 to 5.0 micro g per well. Activity is sensitive to known PDH inhibitors and remains regulated by phosphorylation and dephosphorylation after immunopurification because of the presence of bound PDH kinase(s) and phosphatase(s). It is shown that the immunocapture assay can be used to detect PDH deficiency in cell extracts of cultured fibroblasts from patients, making it useful in patient screens, as well as in the high-throughput format for discovery of new modulators of PDH functioning.
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PMID:Immunocapture and microplate-based activity measurement of mammalian pyruvate dehydrogenase complex. 1263 10

Sir2 is a NAD(+)-dependent histone deacetylase that controls gene silencing, cell cycle, DNA damage repair, and life span. Prompted by the observation that the [NAD(+)]/[NADH] ratio is subjected to dynamic fluctuations in skeletal muscle, we have tested whether Sir2 regulates muscle gene expression and differentiation. Sir2 forms a complex with the acetyltransferase PCAF and MyoD and, when overexpressed, retards muscle differentiation. Conversely, cells with decreased Sir2 differentiate prematurely. To inhibit myogenesis, Sir2 requires its NAD(+)-dependent deacetylase activity. The [NAD(+)]/[NADH] ratio decreases as muscle cells differentiate, while an increased [NAD(+)]/[NADH] ratio inhibits muscle gene expression. Cells with reduced Sir2 levels are less sensitive to the inhibition imposed by an elevated [NAD(+)]/[NADH] ratio. These results indicate that Sir2 regulates muscle gene expression and differentiation by possibly functioning as a redox sensor. In response to exercise, food intake, and starvation, Sir2 may sense modifications of the redox state and promptly modulate gene expression.
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PMID:Sir2 regulates skeletal muscle differentiation as a potential sensor of the redox state. 1291 68

The effects of increasing mitochondrial oxidative phosphorylation (OXPHOS), by enhancing electron transport chain components, were evaluated on 1-methyl-4-phenylpyridinium (MPP+) toxicity in brain neuroblastoma cells. Although glucose is a direct energy source, ultimately nicotinamide and flavin reducing equivalents fuel ATP produced through OXPHOS. The findings indicate that cell respiration/mitochondrial O(2) consumption (MOC) (in cells not treated with MPP+) is not controlled by the supply of glucose, coenzyme Q(10) (Co-Q(10)), NADH+, NAD or nicotinic acid. In contrast, MOC in whole cells is highly regulated by the supply of flavins: riboflavin, flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN), where cell respiration reached up to 410% of controls. In isolated mitochondria, FAD and FMN drastically increased complex I rate of reaction (1300%) and (450%), respectively, having no effects on complex II or III. MPP+ reduced MOC in whole cells in a dose-dependent manner. In isolated mitochondria, MPP+ exerted mild inhibition at complex I, negligible effects on complexes II-III, and extensive inhibition of complex IV. Kinetic analysis of complex I revealed that MPP+ was competitive with NADH, and partially reversible by FAD and FMN. Co-Q(10) potentiated complex II ( approximately 200%), but not complex I or III. Despite positive influence of flavins and Co-Q(10) on complexes I-II function, neither protected against MPP+ toxicity, indicating inhibition of complex IV as the predominant target. The nicotinamides and glucose prevented MPP+ toxicity by fueling anaerobic glycolysis, evident by accumulation of lactate in the absence of MOC. The data also define a clear anomaly of neuroblastoma, indicating a preference for anaerobic conditions, and an adverse response to aerobic. An increase in CO(2), CO(2)/O(2) ratio, mitochondrial inhibition or O(2) deprivation was not directly toxic, but activated metabolism through glycolysis prompting depletion of glucose and starvation. In conclusion, the results of this study indicate that the mechanism of action for MPP+, involves the inhibition of complex I and and more specifically complex IV, leading to impaired OXPHOS and MOC. Moreover, flavin dervatives control the rate of complex I/cellular respiration and Co-Q10 augments complex II [corrected].
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PMID:Effects of enhancing mitochondrial oxidative phosphorylation with reducing equivalents and ubiquinone on 1-methyl-4-phenylpyridinium toxicity and complex I-IV damage in neuroblastoma cells. 1500 52


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