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)

The oligomeric small heat-shock protein hsp27, also denoted hsp28, is constitutively expressed in several mammalian cells and displays a phosphorylation status that is related to cellular growth and differentiation. This protein is related to alpha-crystallin and has strong sequence similarity with an in vitro inhibitor of actin polymerization. Here, we have analyzed hsp27 phosphorylation, cellular localization and structural organization following serum stimulation of serum-starved HeLa cells. hsp27 is dephosphorylated in starved cells and quantitatively recovered in the form of small structures (< 200 kDa) present in the soluble phase of the cytoplasm. Immediately after the addition of serum to starved cells, a rapid phosphorylation and complex changes in the intracellular distribution and structural organization of hsp27 are observed. Phosphorylation essentially occurs at the level of small hsp27 structures (< 200 kDa) and is concomitant with the increased molecular mass (up to 700 kDa) of a fraction of this protein. Serum treatment also induced the detergent-sensitive association of another fraction of hsp27, still in the form of small and dephosphorylated structures, with cellular particulate fractions. Contrasting with these observations, hsp70 had the tendency to concentrate into nucleoli during serum starvation.
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PMID:The serum-induced phosphorylation of mammalian hsp27 correlates with changes in its intracellular localization and levels of oligomerization. 816 20

The small heat shock protein alphaB-crystallin interacts with intermediate filament proteins. Using a co-sedimentation assay, we showed that in vitro binding of alphaB-crystallin to peripherin and vimentin was temperature-dependent. Specifically, a synthetic peptide representing the first ten residues of alphaB-crystallin was involved in this interaction. When cells were submitted to different stress conditions such as serum starvation, hypertonic stress, or heat shock, we observed a dynamic reorganisation of the intermediate filament network, and concomitant recruitment of alphaB-crystallins on intermediate filament proteins. Under normal conditions alphaB-crystallin was extracted from cells by detergent. In stressed cells, alphaB-crystallin colocalised with intermediate filament proteins, and became resistant to detergent extraction. The intracellular state of alphaB-crystallin seemed to correlate directly with the remodelling of the intermediate filament network in response to stress. This suggested that alphaB-crystallin functions as a molecular chaperone for intermediate filament proteins.
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PMID:AlphaB-crystallin interacts with intermediate filaments in response to stress. 942 92

We previously reported that PKN, a fatty acid-activated serine/threonine protein kinase, translocates from the cytosol to the nucleus by stresses such as heat shock, sodium arsenite, and serum starvation. To clarify the role of PKN under heat stress, we examined whether PKN regulates the expression of heat shock proteins. Co-expression of heat shock transcription factor 1 (HSF1) and the catalytically active fragment of PKN induced the accumulation of alphaB-crystallin but not HSP27 and HSP70 in HeLa S3 cells. The expression of the reporter gene for alphaB-crystallin promoter was activated by co-expression of HSF1 and the catalytically active fragment of PKN, and this activation was dependent on the protein kinase activity of PKN. Deletion analysis of the alphaB-crystallin promoter region revealed that both the proximal and the distal heat shock elements were necessary for the transactivation. These results raise the possibility that there is a signal transduction pathway mediating stress signals for the accumulation of alphaB-crystallin by HSF1 and PKN.
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PMID:The role of PKN in the regulation of alphaB-crystallin expression via heat shock transcription factor 1. 983 46

Oxygen starvation triggers the shiftdown of the obligate aerobe Mycobacterium bovis BCG to a state of dormancy. Two-dimensional electrophoresis showed a drastic up-regulation of the alpha-crystallin homolog, the putative response regulator Rv3133c, and the two conserved hypothetical proteins Rv2623 and Rv2626c in dormant bacilli.
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PMID:Proteins of Mycobacterium bovis BCG induced in the Wayne dormancy model. 1127 29

The cDNA sequence of beta crystallin B1 was determined from zebrafish (Danio rerio) and compared to the corresponding genes of bovine, rat, chicken, human, and Xenopus. Multispecies comparison of superfamily diversity demonstrated beta crystallin B1 homology between zebrafish, bovine, chicken, and rat, but large distances to beta crystallin B2 and B3. Zebrafish cDNA has a size of 943 nucleotides and encodes a polypeptide of 233 amino acids. Zebrafish beta crystallin B1 shares 71.30, 75.86, and 71.00% similarities with bovine, chicken, and rat beta crystallin B1, respectively. Northern blot analysis revealed a single 0.9-kb beta crystallin B1 transcript which was expressed and progressively increased in the first 20 h of zebrafish embryogenesis. Whole-mount in situ hybridization revealed that the beta crystallin B1 transcript was only specifically expressed in the lens region of the eye. A starvation experiment revealed no variation in mRNA levels after 14 and 21 days. An experiment in which hormone was injected showed that the beta crystallin B1 transcript first increased 24 h after the injection of insulin-like growth factor I, insulin-like growth factor II, or growth hormone, then decreased 48 h after injection. The beta crystallin B1 transcript continuously increased after insulin was injected. Taken together, our results identify the early specific expression of beta crystallin B1 within the lens. Despite small differences, these results indicate that both the structure of the beta crystallin B1 protein and its involvement with regulation by growth factors appear to have been remarkably conserved.
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PMID:Molecular cloning, developmental expression, and hormonal regulation of zebrafish (Danio rerio) beta crystallin B1, a member of the superfamily of beta crystallin proteins. 1143 79

Obligately aerobic tubercle bacilli are capable of adapting to survive hypoxia by developing into a nonreplicating or dormant form. Dormant bacilli maintain viability for extended periods. Furthermore, they are resistant to antimycobacterials, and hence, dormancy might play a role in the persistence of tuberculosis infection despite prolonged chemotherapy. Previously, we have grown dormant Mycobacterium bovis BCG in an oxygen-limited Wayne culture system and subjected the bacilli to proteome analysis. This work revealed the upregulation of the response regulator Rv3133c and three other polypeptides (alpha-crystallin and two "conserved hypothetical" proteins) upon entry into dormancy. Here, we replaced the coding sequence of the response regulator with a kanamycin resistance cassette and demonstrated that the loss-of-function mutant died after oxygen starvation-induced termination of growth. Thus, the disruption of this dormancy-induced transcription factor resulted in loss of the ability of BCG to adapt to survival of hypoxia. Two-dimensional gel electrophoresis of protein extracts from the gene-disrupted strain showed that the genetic loss of the response regulator caused loss of the induction of the other three dormancy proteins. Thus, the upregulation of these dormancy proteins requires the response regulator. Based on these two functions, dormancy survival and regulation, we named the Rv3133c gene dosR for dormancy survival regulator. Our results provide conclusive evidence that DosR is a key regulator in the oxygen starvation-induced mycobacterial dormancy response.
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PMID:Mycobacterium bovis BCG response regulator essential for hypoxic dormancy. 1244 25

We identified a response regulator in Mycobacterium smegmatis which plays an important role in adaptation to oxygen-starved stationary phase. The regulator exhibits strong sequence similarity to DevR/Rv3133c of M. tuberculosis. The structural gene is present on a multigene locus, which also encodes a sensor kinase. A devR mutant of M. smegmatis was adept at surviving growth arrest initiated by either carbon or nitrogen starvation. However, its culturability decreased several orders of magnitude below that of the wild type under oxygen-starved stationary-phase conditions. Two-dimensional gel analysis revealed that a number of oxygen starvation-inducible proteins were not expressed in the devR mutant. Three of these proteins are universal stress proteins, one of which is encoded directly upstream of devR. Another protein closely resembles a proposed nitroreductase, while a fifth protein corresponds to the alpha-crystallin (HspX) orthologue of M. smegmatis. None of the three universal stress proteins or nitroreductase, and a considerably lower amount of HspX was detected in carbon-starved wild-type cultures. A fusion of the hspX promoter to gfp demonstrated that DevR directs gene expression when M. smegmatis enters stationary phase brought about, in particular, by oxygen starvation. To our knowledge, this is the first time a role for a two-component response regulator in the control of universal stress protein expression has been shown. Notably, the devR mutant was 10(4)-fold more sensitive than wild type to heat stress. We conclude that DevR is a stationary-phase regulator required for adaptation to oxygen starvation and resistance to heat stress in M. smegmatis.
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PMID:A two-component regulator of universal stress protein expression and adaptation to oxygen starvation in Mycobacterium smegmatis. 1259 71

Mycobacterium tuberculosis is able to persist in the human host for decades in an apparently dormant state where it is presumed to reside in an hypoxic environment. This can be mimicked by the Wayne culture model in which progressive oxygen depletion causes the bacteria to shift into a non-replicating state. We investigated global gene expression in aerobic (roller), microaerophilic (NRP1) and anaerobic (NRP2) cultures. A number of genes were significantly up-regulated as compared to aerobic culture; 178 in NRP1, 210 in NRP2, 88 in both. The two states showed distinct gene expression profiles, although a number of membrane and transmembrane proteins were induced in both conditions. A number of regulatory proteins were up-regulated in NRP2. Glycine dehydrogenase, nitrate reductase and alpha-crystallin were induced in both stages, as were fatty acid metabolism genes including fadD26 and mas and genes of the DosR regulon. In a comparison with other stress conditions, there were more similarities between anaerobic conditions and carbon starvation or heat shock than between microaerophilic conditions and carbon starvation or heat shock, but as expected microaerophilic and anaerobic conditions showed the most similar profile. Our results indicate that a large number of genes are up-regulated during the shift into the persistent state.
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PMID:Gene expression profile of Mycobacterium tuberculosis in a non-replicating state. 1520 93

alphaA- and alphaB-crystallins are small heat shock proteins and molecular chaperones that are known to prevent non-specific aggregation of denaturing proteins. Recent work indicates that alphaA-/- lens epithelial cells grow at a slower rate than wild-type cells, and cultured alphaB-/- cells demonstrate increased hyperproliferation and genomic instability, suggesting that these proteins may exert a direct effect on the cell cycle kinetics, and influence cell proliferation. However, the cell cycle parameters of alphaA/alphaBKO (double knockout) cells have not been analyzed. Here we investigate the cell cycle kinetics of synchronized mouse lens epithelial cultures derived from wild-type and alphaA/alphaB double knockout (alphaA/alphaBKO) mice using BrdU labeling of proliferating cells, and flow cytometric analysis. We also provide data on the changing pattern of expression of HSP25, a small heat shock protein in alphaA/alphaBKO and wild-type cells during the cell cycle. Using serum starvation to synchronize cells in the quiescent G0 phase, and restimulation with serum followed by BrdU labeling and flow cytometry, the data indicated that as compared to wild-type cells, a <50% smaller fraction of the alphaA/alphaBKO cells entered the DNA synthetic S phase of the cell cycle. Furthermore, there was a delay in cell cycle transit through S phase in alphaA/alphaBKO cells, suggesting that although capable of entering S phase, the alphaA/alphaBKO cells are blocked in G1 phase, and are delayed in their cell cycle progression. Immunoblot analysis with antibodies to the small heat shock protein HSP25 indicated that although HSP25 increased in G1 phase of wild-type cells, and remained elevated on further progression through the cell cycle, HSP25 accumulation was delayed to S phase in alphaA/alphaBKO cells. These data can be interpreted to indicate that mouse lens epithelial cell progression through the cell cycle is significantly affected by expression of alphaA and alphaB-crystallin.
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PMID:Cell kinetic status of mouse lens epithelial cells lacking alphaA- and alphaB-crystallin. 1554 41

AlphaA- and alphaB-crystallins are small heat shock proteins and molecular chaperones that prevent non-specific aggregation of denaturing proteins. Previous work in our laboratory has shown that lens epithelial cells derived from alphaA-/- mice exhibit slower growth, whereas alphaB-/- lens epithelial cells hyperproliferate at a higher rate in culture [Andley et al., J. Biol. Chem. 273 (1998) 31252; FASEB J. 15 (2001) 221]. Although both have been implicated in apoptosis and cell proliferation, direct analysis of their expression during the cell cycle has not been investigated. This study was undertaken to define the expression levels of alphaA and alphaB-crystallins during the cell cycle. Primary lens epithelial cell cultures derived from wild type mice were synchronized by serum starvation, and pulsed with bromodeoxyuridine (BrdU) at different times after re-stimulation with serum. Dual parameter flow cytometric studies with BrdU and propidium iodide (PI)-labeled cells were performed. Cells entered S phase 14 hr after serum re-stimulation. The duration of the S phase was 6 hr, and the total cell cycle transit time was between 24-27 hr. Enhanced expression of cyclin A, a protein essential for DNA synthesis was used as an additional marker to define the initiation of the S phase. Immunoblotting analysis demonstrated that the expression of alphaA and alphaB-crystallin was up to 10-fold higher in cells synchronized in G0 phase than in G1 phase. The levels of the proteins increased three-fold again as the cells entered the S phase and progressed to mitosis, but did not rise to the levels observed in G0 phase. This increase in expression of alphaA-crystallin resulted in part from enhanced synthesis during the S phase, as shown by an increase in [35S]methionine-labeling and immunoprecipitation of the radiolabeled alphaA-crystallin. The results were further confirmed by flow cytometric analysis using DNA content and alphaA-crystallin expression. The increase in alphaB-crystallin in S phase was paralleled by an increase in gene expression as shown by real-time RT-PCR analysis. These results demonstrate for the first time that in lens epithelial cells, alphaA and alphaB-crystallin levels are modulated during the cell cycle. Since the absence of alphaA and alphaB- crystallin in lens epithelial cells has been associated with disturbance of the tubulin cytoskeleton during mitosis, and with increased cell death or genomic instability, our results indicating that the alphaA- and alphaB-crystallin expression increases prior to mitosis are significant. The differential expression of these crystallins in the cell cycle may be important for optimal lens epithelial growth and lens transparency.
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PMID:A comparative analysis of alphaA- and alphaB-crystallin expression during the cell cycle in primary mouse lens epithelial cultures. 1564 16


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