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)

Tryptophan was measured in the cisternal CSF and brains of rats. In untreated rats there was a significant but not very close correlation between the tryptophan concentration in these two compartments. Factors that change the brain tryptophan concentration such as starvation, glucose feeding, and lithium treatment affected the CSF tryptophan in the same way as the brain tryptophan. Diurnal changes were parallel for brain and CSF. When we take into account our knowledge of the disposition of tryptophan in human CSF, these data suggest that measurement of lumbar CSF tryptophan in man may be a useful approach to the study of human brain tryptophan. However, because the correlation between brain and CSF is not very close, measurements on CSF tryptophan would be more meaningful in groups of patients than in individuals.
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PMID:Relationship between rat brain and cisternal CSF tryptophan concentrations. 94 32

The mechanisms by which riboflavin, which is not synthesized in mammals, enters and leaves brain, CSF, and choroid plexus were investigated by injecting [14C]riboflavin intravenously or intraventricularly. Tracer amounts of [14C]riboflavin with or without FMN were infused intravenously at a constant rate into normal, starved, or probenecid-pretreated rabbits. AT 3 h, [14C]riboflavin readily entered choroid plexus and brain, and, to a much lesser extent, CSF. Over 85% of the [14C]riboflavin in brain and choroid plexus was present as [14C]FMN and [14C]FAD. The addition of 0.2 mmol/kg FMN to the infusate markedly depressed the relative entry of [14C]riboflavin into brain, choroid plexus, and, less so, CSF, whereas starvation increased the relative entry of [14C]riboflavin into brain and choroid plexus. After intraventricular injection (2 h), most of the [14C]riboflavin was extremely rapidly cleared from CSF into blood. Some of the [14C]riboflavin entered brain, where over 85% of the 14C was present as [14C]FMN plus [14C]FAD. The addition of 1.23 mumol FAD (which was rapidly hydrolyzed to riboflavin) to the injectate decreased the clearance of [14C]riboflavin from CSF and the phosphorylation of [14C]riboflavin in brain. Probenecid in the injectate also decreased the clearance of [14C]riboflavin from CSF. These results show that the control of entry and exit of riboflavin is the mechanism, at least in part, by which total riboflavin levels in brain cells and CSF are regulated. Penetration of riboflavin through the blood-brain barrier, saturable efflux of riboflavin from CSF, and saturable entry of riboflavin into brain cells are three distinct parts of the homeostatic system for total riboflavin in the central nervous system.
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PMID:Riboflavin homeostasis in the central nervous system. 745 54

With erythroid differentiation, committed progenitor cells acquire the ability to respond to erythropoietin (Epo). Epo interacts with target cells through the Epo receptor (Epo-R), whose expression is tightly regulated in a lineage-specific fashion. Epo-R expression is presumed to be progressively activated or repressed as cells progress along the erythroid or the myeloid pathway, respectively. Little is known of the mechanisms that underlie the erythroid-specific expression of the Epo-R gene. GATA-1, the major known transcription factor involved in Epo-R gene regulation, is not erythroid-specific. We have studied the regulation of the expression of the Epo-R gene in two related human Epo-responsive cell lines, UT-7 and UT-7 Epo. These lines express Epo-R at high levels because of amplification of the endogenous gene, which is apparently not rearranged. Treatment for 6 to 24 hours with the tumor promoter, phorbol myristate acetate (PMA), or 24 hours of growth factor starvation (Epo or granulocyte/macrophage colony-stimulating factor [GM-CSF]) decreased or increased the levels of Epo-R mRNA, respectively. In the case of growth factor starvation, the increase (approximately equal to threefold) in the level of Epo-R mRNA correlated directly with an increase in the rate of Epo-R gene transcription as measured by run-off assay. Both increases were observed as early as 3 hours after the growth factor was withdrawn and were reversible; levels of mRNA and transcription rates returned to baseline 3 hours after the cells were reexposed to growth factors. The changes in Epo-R expression after growth factor starvation were coordinated with changes in the level of expression of GATA-1 that were detected both at the mRNA and at the gene transcription level under these conditions (suggesting that GATA-1 was responsible for this upregulation). During PMA treatment, after a transient increase in Epo-R mRNA at 1 hour, a progressive decline in the level of Epo-R mRNA was observed; the level of Epo-R mRNA decreased by 50%, and fell below the level of detection by 6 and 24 hours, respectively. This decrement was explained in part by a fourfold reduction in the rate of gene transcription as well as a reduction (measured as levels of Epo-R mRNA in the presence of actinomycin D) in mRNA stability. The changes in transcription rate occurred in the absence of changes in the level of GATA-1 binding activity.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Transcriptional and posttranscriptional regulation of the expression of the erythropoietin receptor gene in human erythropoietin-responsive cell lines. 826 Jul 13

Thrombopoietin (TPO) has been demonstrated to have proliferative effects on hematopoietic progenitor cells and maturational effects on more committed populations which express a megakaryocyte lineage-specific phenotype. M07e is a GM-CSF or interleukin 3 (IL-3)-dependent human leukemic cell line having surface markers characteristic of both myeloid progenitors and megakaryocytes. The effects of TPO on the proliferation and survival of M07e cells were investigated. Following an 18-h factor starvation period to remove residual growth factor signals and phase the cells in G0/G1, TPO provides a weak proliferative signal to M07e compared to IL-3 or GM-CSF treatment under the same conditions. However, TPO synergizes with both GM-CSF and IL-3, and to a greater extent with steel factor, a competence factor for M07e, in the induction of cellular proliferation. TPO sustains cellular integrity of M07e during prolonged (18 days) growth factor withdrawal and also protects M07e cells in serum-free conditions. In addition, preincubation of M07e for 72 h in TPO maintains its survival for subsequent cytokine-induced proliferation, while control media do not. TPO suppresses growth factor withdrawal-induced apoptosis as evaluated by flow cytometric detection of both in situ terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling and cellular DNA content via propidium iodide staining. These results suggest a role for TPO as a survival factor for M07e cells.
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PMID:Thrombopoietin suppresses apoptosis and behaves as a survival factor for the human growth factor-dependent cell line, M07e. 872 99

We have analyzed the effects of IL-15, a growth factor with IL-2-like properties produced by dendritic and stromal cells, on 3 GM-CSF/IL-3-dependent AML cell lines: M-07e, UT-7 and TF-1. M-07e cells proliferated in response to IL-15, while UT-7 and TF-1 cells failed to respond. In addition, IL-15 supported long-term proliferation of M-07e cells, thus allowing selection of a subline (M-07SB), which displayed an enhanced sensitivity to IL-15. M-07e and M-07SB cells undergo apoptosis following 48-hr growth factor (GM-CSF or IL-15) starvation, as detected by cytofluorimetric analysis and DNA laddering. IL-15 (20 ng/ml) prevented apoptosis in both cell lines. M-07e and M-07SB expressed IL-2R beta, IL-2R gamma, Jak-1 and Jak-3 mRNA, while IL-15R alpha mRNA was undetectable. In contrast, IL-15R alpha was expressed in UT-7 and TF-1 cells, which lacked expression of IL-2R beta mRNA and, in the case of UT-7, also of Jak-3 mRNA. Accordingly, surface IL-2R beta protein was identified only in M-07e and M-07SB cells, by indirect immunofluorescence, while no expression of IL-2R alpha and IL-15R alpha was detected. Anti-IL-2R beta antibodies (10 microg/ml) efficiently blocked (90% inhibition) the proliferation and the anti-apoptotic effect induced by IL-15, while anti-GM-CSFR alpha antibodies had no effect. Anti-IL-2R gamma antibodies were less efficient at proliferation inhibition but synergized with suboptimal concentrations of anti-IL-2R beta antibodies. Our data suggest a role of IL-15 as an anti-apoptotic and mitogenic growth factor for a subset of myeloid leukemias expressing a functional IL-2R beta/gamma complex.
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PMID:Interleukin (IL)-15 induces survival and proliferation of the growth factor-dependent acute myeloid leukemia M-07e through the IL-2 receptor beta/gamma. 975 51

Recombinant human granulocyte-macrophage colony stimulating factor (hGM-CSF) has been previously produced in tobacco cell suspension cultures. However, the amount of hGM-CSF accumulated in the culture medium dropped quickly from its maximum of 150 microg/L at 5 d after incubation. To overcome this problem, we sought an expression system in which heterologous gene expression could be induced at high levels. We selected a rice amylase expression system in which the promoter Ramy3D is induced to express recombinant protein by sucrose starvation. This induction system was found to give good yield of recombinant hGM-CSF in transgenic rice cell suspension culture and protease activity of this culture medium was low compared to that of tobacco culture system.
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PMID:High level of expression of recombinant human granulocyte-macrophage colony stimulating factor in transgenic rice cell suspension culture. 1270 Nov 43

Human granulocyte-colony stimulating factor (hG-CSF), a human cytokine, was expressed in transgenic rice cell suspension culture. The hG-CSF gene was cloned into the rice expression vector containing the promoter, signal peptide, and terminator derived from a rice alpha-amylase gene Amy3D. Using particle bombardment-mediated transformation, hG-CSF gene was introduced into the calli of rice (Oryza sativa) cultivar Dong-jin. Expression of the hG-CSF gene was confirmed by ELISA and Northern blot analysis. The amount of recombinant hG-CSF accumulated in culture medium from transgenic rice cell suspension culture on the sugar starvation was determined by time series ELISA. Biological activity of the plant derived hG-CSF was confirmed by measuring the proliferation of the AML-193 cells, and was similar to that of the commercial Escherichia coli-derived hG-CSF. In this paper, we discuss the attractive attributes of using rice cell suspension system for the expression of therapeutic recombinant hG-CSF.
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PMID:Production of bioactive human granulocyte-colony stimulating factor in transgenic rice cell suspension cultures. 1629 43

The influence of environmental factors (cytokines, matrix components, serum factors and O(2) level) on expression of receptors for angiogenic versus angiostatic CXC chemokines in human microvascular endothelial cells has not been extensively investigated. Our semi-quantitative RT-PCR analysis demonstrated that TNF-alpha and IFN-gamma repressed CXCR4 mRNA levels in immortalized human microvascular endothelial HMEC-1 cells after 4 h, whereas only TNF-alpha displayed inhibitory activity in primary human microvascular endothelial cells (HMVEC). CXCR4 mRNA expression was not affected by VEGF, GM-CSF, IL-1beta or various basal membrane matrix components, but was significantly up-regulated after serum starvation and/or hypoxic treatment of the microvascular endothelial cells. The alternative CXCL12 receptor, CXCR7/RDC1, was also up-regulated by hypoxia in HMEC-1 cells, although less consistently than CXCR4. Furthermore, hypoxia and serum starvation were required for cell surface display of CXCR4 and CXCL12 induction of ERK activation in HMEC-1 cells. In contrast, CXCR2 and CXCR3 mRNA levels remained, respectively, low and undetectable under all the conditions tested, and surface expression of CXCR2, CXCR3 and CXCR7 on the HMEC- 1 cells could not be demonstrated by FACS. In the human SK-MEL-5 melanoma cell line, CXCR4 mRNA expression was also increased under hypoxic conditions, whereas CXCR2 mRNA levels remained low and levels of CXCR3 and CXCR7 were undetectable. However, immunohistochemical staining of human metastatic melanoma sections demonstrated that CXCR2, CXCR3, CXCR4 and CXCR7 are expressed on tumor cells and, to a lesser extent, on endothelial cells. These results demonstrate that the tumor microenvironment regulates chemokine receptor expression through both cytokine and oxygen levels.
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PMID:Hypoxia enhances CXCR4 expression in human microvascular endothelial cells and human melanoma cells. 1759 38

Recombinant proteins have been previously synthesized in a transgenic rice cell suspension culture system with the rice amylase 3D promoter, which can be induced via sugar starvation. However, the secreted recombinant proteins have been shown to be rapidly decreased as the result of proteolytic degradation occurring during prolonged incubation. The secreted proteases were identified via two-dimensional electrophoresis (2-DE) and ESI/Q-TOF mass spectrometry analyses. The internal amino acid sequences of 8 of 37 spots corresponded to cysteine proteinase (CysP), which is encoded for by Rep1 and EP3A. This result shows that CysP is a major secreted protease in rice cell suspension cultures following induction via sugar starvation. Intron-containing self-complementary hairpin RNA (ihpRNA)-mediated post-transcriptional gene silencing (PTGS) was applied to suppress the expression of CysP in rice cell suspension cultures. The reduction of rice CysP mRNA and the detection of siRNA specific to CysP, an initiator of RNAi, were verified via Northern blot analysis and RNase protection assays, respectively, thereby indicating that PTGS operated successfully in this system. The analysis of total secreted protease and CysP activities evidenced lower activity than was observed with the wild-type. Furthermore, suspension cultures of rice cells transformed with both hGM-CSF and the gene expressing the ihpRNA of CysP evidenced a reduction in total protease and CysP activities, and an up to 1.9-fold improvement in hGM-CSF production as compared to that observed in a rice cell line expressing hGM-CSF only. These results demonstrate the feasibility of the suppression of CysP via RNA interference to reduce protease activity and to increase target protein accumulation in rice cell suspension cultures.
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PMID:Improvement of recombinant hGM-CSF production by suppression of cysteine proteinase gene expression using RNA interference in a transgenic rice culture. 1858 53

A rice cell suspension culture system with the Ramy3D promoter, which is induced by sucrose starvation, has been previously utilized to produce large quantities of recombinant proteins. Although this expression system was reported previously to generate a good yield of recombinant hGM-CSF in transgenic rice cell suspension culture, rice alpha-amylase was a dominant protein, with 43% of total secreted proteins and an obstacle to the production and purification of secreted recombinant proteins in a rice cell suspension culture. In this study, an intron-containing self-complementary hairpin RNA (ihpRNA)-mediated post transcriptional gene silencing (PTGS) strategy for the rice alpha-amylase gene was applied in order to overcome this problem in rice cell suspension culture systems. The reduction of the mRNA level of the rice alpha-amylase gene was verified via Northern blot analysis and siRNA, an initiator of RNA interference, was detected via an RNase protection assay. The amount of rice alpha-amylase in the culture medium was reduced to 8.2% as compared to that of the wild-type. A transgenic rice cell suspension culture expressing both the hGM-CSF and ihpRNA of the rice alpha-amylase gene demonstrated that the quantity of rice alpha-amylase was reduced to 22% and that the accumulation of hGM-CSF increased by 1.9-fold as compared to that in the transgenic cell line expressing hGM-CSF only. These results indicated that RNAi technology should be of great utility for suppressing undesirable genes, and should improve accumulation and facilitate the purification of secreted recombinant proteins in rice cell suspension cultures.
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PMID:Amylase gene silencing by RNA interference improves recombinant hGM-CSF production in rice suspension culture. 1863 17


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