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

Fibroblast growth factor-2 (FGF-2) is a potent autocrine mitogen for fetal epiphyseal growth plate chondrocytes and exhibits a transient nuclear translocation during G1 of the cell cycle. We have characterized an intracellular binding protein (FGFBP) for FGF-2 that undergoes a juxtanuclear localization coincident with the nuclear translocation of the growth factor. Chondrocytes were isolated from the proliferative zone of the ovine fetal proximal tibial growth plate at 50-130 days gestation by collagenase digestion and were maintained in monolayer at early passage number. Cells were growth restricted by serum starvation for 48 h, and the synchronized culture was restarted into the cell cycle in the presence of 2% FBS. Cells were removed between 4-26 h of incubation, and fractions representing the plasma membrane, cytoplasm, nuclear membrane, and nuclear contents were separated by differential centrifugation. FGFBPs were separated using FGF-2 affinity chromatography. Ligand blot analysis using 125I-labeled FGF-2 showed that a FGFBP of 46-48 kDa (represented by a double band) was present on the nuclear membrane at mid to late G1, and Western blot showed this to be immunologically related to a part of the extracellular domain of the high affinity FGF receptor 1 (FGFR1). Immunocytochemistry with intact cell cultures showed that this protein underwent a juxtanuclear distribution through mid to late G1. Immunoprecipitation was performed to monitor newly synthesized FGFR1 migration throughout the cell cycle. Synchronized cells were cultured in medium containing 35S-labeled methionine/cysteine, and the cellular compartments were separated before immunoprecipitation using an antibody raised against the extracellular domain of FGFR1. Newly synthesized FGFR1-related proteins appeared throughout G1 and migrated multidirectionally within the cell; intact receptor of 125-145 kDa accumulated at the plasma membrane, while both intact receptor and truncated FGFR1 of 46-48 kDa were detected on the nuclear membrane, but not within the nucleus. Cells were incubated with protamine sulfate to prevent the binding of endogenous, cell membrane-associated FGF-2 to high affinity FGFRs and their subsequent internalization. This did not alter the juxtanuclear accumulation of truncated FGFR1 in late G1, suggesting that this was not derived from the plasma membrane. The truncated FGFR1 may mediate the nuclear translocation of FGF-2 during late G1.
 ...
PMID:Perinuclear localization of an intracellular binding protein related to the fibroblast growth factor (FGF) receptor 1 is temporally associated with the nuclear trafficking of FGF-2 in proliferating epiphyseal growth plate chondrocytes. 889 82

Tumor cells exposed to a growth stress such as low pH, glucose starvation and hypoxia have been shown to exhibit a transient increase in experimental metastatic potential, particularly when allowed to recover under normal growth conditions for a period of 24-48 h. In this study we examined whether this increase in metastatic ability could be explained by changes in the expression of a number of different metastasis-associated genes, when the cells were exposed to similar conditions (24-48 h exposure to the stress condition followed by 0-48 h recovery under normal growth conditions). Although the cell lines used (KHT fibrosarcoma, SCC VII squamous cell carcinoma, and B16F1 melanoma) demonstrated altered metastatic ability after the treatment, no overall temporal correlation between changes in the mRNA levels for cathepsin B, cathepsin L, nm23, TIMP-1, osteopontin, or VEGF and metastatic ability in the three cell lines was observed. The production of gelatinase A (72 kDa collagenase) and gelatinase B (92 kDa collagenase) was also measured by gelatin zymography. There was an increase in production of these enzymes with increasing recovery time, but it did not parallel changes in metastatic potential. Although these results suggest that the products of most of the genes studied may not be involved in the transient metastatic changes, further studies are required to establish whether changes in protein levels track with changes in mRNA levels for these genes.
 ...
PMID:An examination of the effects of hypoxia, acidosis, and glucose starvation on the expression of metastasis-associated genes in murine tumor cells. 924 50

The signal transduction cascade initiated by the activation of phosphoinositide 3-kinase (PI-3 kinase) is implicated in mitogenic and antiapoptotic signaling generated by growth factors in a variety of cell types. We have examined the consequences of an inhibition of this pathway in human diploid fibroblasts. We find that a specific PI-3 kinase inhibitor (LY294002) causes growth arrest in these cells accompanied by changes in gene expression that are similar to those seen during cellular senescence. A second inhibitor, PD58029, which is specific for the mitogen-activated protein kinase kinase 1 (MEK-1), also induces a growth arrest but does not induce the same spectrum of gene expression. The pattern of gene expression in the presence the MEK-1 inhibitor is similar to that seen during growth arrest induced by serum starvation. The specific phenotypic changes seen following inhibition of PI-3 kinase are: an increase in beta-galactosidase activity; a decrease in EPC-1 gene expression; and a dramatic increase in collagenase gene expression. Thus, growth arrest with a PI-3 kinase inhibitor induces a senescent-like phenotype that is not seen when cells are growth arrested by either serum starvation or a MEK-1 inhibitor.
 ...
PMID:A phosphatidylinositol 3-kinase inhibitor induces a senescent-like growth arrest in human diploid fibroblasts. 981 8

The function of ovarian interstitial cells has been largely addressed using rat theca-interstitial cell culture. However, this preparation is primarily enriched with theca and secondary interstitial cells, which make it difficult to address selectively the function of the primary interstitial cells. We have developed an in vitro culture of hamster ovarian primary interstitial cells. Cells were isolated from postnatal hamster ovaries by collagenase digestion and purified over a Percoll gradient. The preparation contained 90% viable, pure interstitial cells, which anchored to the plastic and glass culture surface in the presence of fetal bovine serum. Cell proliferation was noted in the presence of serum dosages higher than 0.2%; however, reduction of serum concentration to 0.1% or complete serum starvation did not affect cell viability but almost completely abolished cell proliferation as determined by [3H]thymidine incorporation, labeling index, and DNA content of the culture. All cells exhibited active 3beta-hydroxysteroid dehydrogenase and P450 side chain cleavage immunoreactivity, which corresponded to basal progesterone and androstenedione accumulation. Replacement of serum to starving cells resulted in the induction of the "S" phase and "M" phase specific cyclins, and resumption of cell proliferation. Our results indicate that hamster primary interstitial cells can be cultured in vitro as a monolayer, and the anchorage and proliferation of these cells depend on serum supplement; however, a viable monolayer can be maintained for several days without serum. This model will be useful for addressing the mechanisms of differentiation of ovarian interstitial cells.
 ...
PMID:In vitro culture of hamster ovarian primary interstitial cells: effect of serum. 978 Mar 26

Both exhaustive physical exertion and starvation have been reported to induce depression of immune function. The aim of the present study was to investigate the inflammatory environment and state of activation and mediator-producing potential of circulating leukocytes during prolonged physical activity with concomitant energy and sleep deprivation. Eight well-trained males were studied during 7 days of semi-continuous physical activity. Sleep was restricted to about 1 h/24 h, energy intake to 1.5- 3.0 MJ/24 h. Blood was drawn at 07.00 A.M.: on days 0, 2, 4, and 7. Plasma levels of inflammation markers were measured. The response of circulating leukocytes to lipopolysaccharide (LPS; 1 microg mL(-1)), and the effect of added hydrocortisone (10 and 100 nmol L(-1)), were measured in the supernatant after 3 h of incubation in an ex vivo whole blood model. Activation of leukocytes steadily increased as measured by plasma matrix metalloproteinase-9, tumour necrosis factor-alpha, interleukin-1beta, and interleukin-6. Inhibitors of systemic inflammation were either unaltered (tissue inhibitor of matrix metalloproteinase-1) or elevated (plasma interleukin-1 receptor antagonist). Cortisol levels increased on days 2 and 4, but thereafter reverted to baseline values. The leukocytes responded to LPS activation with increasing release of inflammatory cytokines throughout the study period. The anti-inflammatory potency of hydrocortisone decreased. Prolonged multifactorial stress thus activated circulating immune cells and primed them for an increased response to a subsequent microbial challenge.
 ...
PMID:Seven days' around the clock exhaustive physical exertion combined with energy depletion and sleep deprivation primes circulating leukocytes. 1650 59

Several studies have already described the presence of specialized niches of precursor cells in vasculature wall, and it has been shown that these populations share several features with mesenchymal stromal cells (MSCs). Considering the relevance of MSCs in the cardiovascular physiopathology and regenerative medicine, and the usefulness of the pig animal model in this field, we reported a new method for MSC-like cell isolation from pig aorta. Filling the vessel with a collagenase solution for 40 min, all endothelial cells were detached and discarded and then collagenase treatment was repeated for 4 h to digest approximately one-third of the tunica media. The ability of our method to select a population of MSC-like cells from tunica media could be ascribed in part to the elimination of contaminant cells from the intimal layer and in part to the overnight culture in the high antibiotic/antimycotic condition and to the starvation step. Aortic-derived cells show an elongated, spindle shape, fibroblast-like morphology, as reported for MSCs, stain positively for CD44, CD56, CD90, and CD105; stain negatively for CD34 and CD45; and express CD73 mRNA. Moreover, these cells show the classical mesenchymal trilineage differentiation potential. Under our in vitro culture conditions, aortic-derived cells share some phenotypical features with pericytes and are able to take part in the formation of network-like structures if cocultured with human umbilical vein endothelial cells. In conclusion, our work reports a simple and highly suitable method for obtaining large numbers of precursor MSC-like cells derived from the porcine aortic wall.
...
PMID:Cells derived from porcine aorta tunica media show mesenchymal stromal-like cell properties in in vitro culture. 2430 32

In vitro cell-based models of lung cancer are frequently employed to study invasion and the mechanisms behind metastasis. However, these models often study only one cell type with two-dimensional (2D) monolayer cell cultures, which do not accurately reflect the complexity of inflammation in vivo. Here, a three-dimensional (3D) cell co-culture collagen gel model was employed, containing human lung adenocarcinoma cells (HCC), human lung fibroblast cells (MRC-5), and macrophages. Cell culture media and cell images were collected, and matrix metalloproteinase-1 (MMP-1) and vascular endothelial growth factor (VEGF) production was monitored under different cell culture conditions. We found that simulating hypoxia and/or serum starvation conditions induced elevated secretion of VEGF in the 3D co-culture model in vitro, but not MMP-1; the morphology of HCC in the 2D versus the 3D co-culture system was extremely different. MMP-1 and VEGF were secreted at higher levels in mixed cell groups rather than mono-culture groups. Therefore, incorporating lung cancer cells, fibroblasts, and macrophages may better reflect physiological metastasis mechanisms compared to mono-culture systems. Tumour stromal cells, macrophages, and fibroblast cells may promote invasion and metastasis, which also provides a new direction for the design of therapies targeted at destroying the stroma of tumor tissues.
...
PMID:Interactions among Lung Cancer Cells, Fibroblasts, and Macrophages in 3D Co-Cultures and the Impact on MMP-1 and VEGF Expression. 2723 98

A major pathway for the detoxification of organic hydroperoxides, such as cumene hydroperoxide (CHP), involves the MarR family transcriptional regulator OhrR and the peroxidase OhrA. However, the effect of these peroxides on the global transcriptome and the contribution of the OhrA/OhrR system to bacterial virulence remain poorly explored. Here, we analyzed the transcriptome profiles of Chromobacterium violaceum exposed to CHP and after the deletion of ohrR, and we show that OhrR controls the virulence of this human opportunistic pathogen. DNA microarray and Northern blot analyses of CHP-treated cells revealed the upregulation of genes related to the detoxification of peroxides (antioxidant enzymes and thiol-reducing systems), the degradation of the aromatic moiety of CHP (oxygenases), and protection against other secondary stresses (DNA repair, heat shock, iron limitation, and nitrogen starvation responses). Furthermore, we identified two upregulated genes (ohrA and a putative diguanylate cyclase with a GGDEF domain for cyclic di-GMP [c-di-GMP] synthesis) and three downregulated genes (hemolysin, chitinase, and collagenase) in the ohrR mutant by transcriptome analysis. Importantly, we show that OhrR directly repressed the expression of the putative diguanylate cyclase. Using a mouse infection model, we demonstrate that the ohrR mutant was attenuated for virulence and showed a decreased bacterial burden in the liver. Moreover, an ohrR-diguanylate cyclase double mutant displayed the same virulence as the wild-type strain. In conclusion, we have defined the transcriptional response to CHP, identified potential virulence factors such as diguanylate cyclase as members of the OhrR regulon, and shown that C. violaceum uses the transcriptional regulator OhrR to modulate its virulence.
 ...
PMID:Global Transcriptional Response to Organic Hydroperoxide and the Role of OhrR in the Control of Virulence Traits in Chromobacterium violaceum. 2850 67

Arginine deprivation is currently being evaluated for its efficacy and safety in clinical trials aimed at combating tumors. However, the cellular signaling and molecular changes in response to such deprivation have not been systematically deciphered. Here, we evaluate the effect of arginine deprivation on human pancreatic cancer cells, with respect to their migratory and invasive potentials and their ability to undergo epithelial-mesenchymal transition (EMT). The transcription factors Snail, Slug, and Twist are regulators of EMT, as indicated by the suppression of E-cadherin and other epithelial markers and adhesion molecules. Our data indicated that arginine starvation inhibited the migration and impaired the adhesion and invasion of the pancreatic cancer cells, decreased Snail, Slug, and Twist expression, and increased E-cadherin expression without altering the expression of vimentin. It is well known that matrix metalloproteinases (MMPs) are important for the events that underlie tumor dissemination. Arginine starvation inhibited the expression of MMP-1 and MMP-9. Furthermore, the PI3K/Akt pathway was altered when the pancreatic cancer cells underwent arginine deprivation as exhibited by the decreased Akt phosphorylation. Thus, these data reveal that arginine deprivation has the potential to decrease the metastatic ability of pancreatic cancer cells.
 ...
PMID:Arginine deprivation inhibits pancreatic cancer cell migration, invasion and EMT via the down regulation of Snail, Slug, Twist, and MMP1/9. 3182 3


<< Previous 1 2