Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.2.1.13 (glyceraldehyde-3-phosphate dehydrogenase)
6,511 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study sought to investigate whether a common protein kinase activity is involved in the sequence of events by which oxygen controls the expression of the genes for erythropoietin (EPO) and for vascular endothelial growth factor (VEGF) in rat hepatocytes. To this end we examined the influence of the non-specific kinase inhibitor staurosporine and of the tyrosine kinase inhibitor genistein on EPO and VEGF mRNA levels in primary cultures of rat hepatocytes kept at either high (20% O2) or low (1% O2) oxygen tension. We found that 3 h of exposure to the low O2 tension increased EPO mRNA levels about 20-fold and the three VEGF (-180, -164, -120) mRNA levels, on average, about fourfold. Staurosporine did not change EPO and VEGF mRNA levels at 20% O2, but in a concentration-dependent manner, decreased EPO and VEGF mRNA at 1% O2 with IC50 values of 30 nM and 1000 nM, respectively. In the presence of 1% O2, genistein decreased EPO mRNA and VEGF mRNA levels with IC50 values of about 36 and 360 microM, respectively. Although mRNA levels for glycerine aldehyde phosphatehydrogenase (GAPDH) were not changed, staurosporine and genistein inhibited uridine incorporation into total RNA with IC50 values of about 1 microM and 100 microM, respectively. Comparison with the transcription inhibitor actinomycin D suggested that the effects of both kinase inhibitors on VEGF mRNA but not on EPO mRNA levels could be attributed to the non-specific inhibition of transcription in hepatocytes. These findings suggest that a kinase activity is specifically involved in the O2-dependent control of EPO gene expression but not of VEGF gene expression in hepatocytes.
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PMID:Differential effects of kinase inhibitors on erythropoietin and vascular endothelial growth factor gene expression in rat hepatocytes. 876 2

Vascular permeability factor, also known as vascular endothelial growth factor (VPF/VEGF), is a disulfide-linked dimeric glycoprotein of about 40 kDa that enhances vascular permeability, induces chemotaxis and activation of monocytes/macrophages, and promotes growth of vascular endothelial cells. It has been reported that several tumor cell lines and normal cells produce VPF/VEGF. To examine the possibility of VPF/VEGF mRNA expression in human peripheral T cells and its mechanism(s) of regulation, we developed a non-radioisotopic semiquantitative reverse transcription-polymerase chain reaction (RT-PCR; VPF/VEGF, GAPDH co-amplification) assay which detects all species of VPF/VEGF mRNA alternative splicing products. T cells expressed negligible VPF/VEGF mRNA in the resting state. However, TPA markedly enhanced the expression of 121-, 165- and 189-amino-acid-containing isoforms of VPF/VEGF mRNA in T cells. Both CD4+ and CD8+ T cells expressed VPF/VEGF mRNA in response to TPA treatment. Moreover, T cell receptor stimulation with monoclonal anti-CD3 antibody with or without IL-1 beta enhanced VPF/VEGF mRNA expression in T cells. These findings suggest that T cell activation induces VPF/VEGF expression in the cells, resulting in induction of its biological activities.
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PMID:Activation-induced expression of vascular permeability factor by human peripheral T cells: a non-radioisotopic semiquantitative reverse transcription-polymerase chain reaction assay. 884 58

Thromboxane A2 (TXA2) is a potent vasoconstrictor which is known to be involved in the pathogenesis of experimental glomerulonephritis, although its exact pathogenic significance is not clear in human glomerulonephritis. We have investigated the expression of thromboxane synthase (TXS) in kidney tissues from patients with IgA nephropathy (IgAN), using RT-PCR and immunohistochemical methods. Biopsied renal tissues from thirty-four patients with IgAN (24 whole tissues and 10 isolated glomeruli) and normal renal tissues from 11 nephrectomized kidneys (control, eight whole tissues and three isolated glomeruli) were included in this study. TXS mRNA expression was observed in 10 out of 24 (42%) whole tissue specimens from IgAN, but no such message was disclosed in the control tissue. There was no detectable TXS mRNA expression in the isolated glomeruli either from IgAN patients or controls, although constant mRNA expressions for GAPDH and VPF/VEGF were observed. IgAN patients with positive TXS mRNA had significantly reduced GFR with elevated serum creatinine and serum beta 2-microglobulin levels. Immunostaining, using a monoclonal anti-TXS antibody, identified the localization of the TXS protein in the interstitial areas where monocyte/macrophage infiltration was abundant, as well as in the arterioles of the kidney tissues with advanced tissue damage. It was concluded that TXA2 produced by the interstitial infiltrating cells during the inflammatory process might be involved in the progression of IgA nephropathy.
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PMID:Expression of thromboxane synthase in kidney tissues from patients with IgA nephropathy. 910 63

In situ hybridization analysis provides a means to qualitatively study the heterogeneity of primary tumors and metastases based on the types of genes transcribed. In this study, we have tested some parameters for quantitative analysis of in situ hybridizations with paraffin-embedded human breast tumors and measured mRNA levels for the angiogenic protein, vascular endothelial growth factor (VEGF). VEGF mRNAs were highly tumor specific, with the highest levels near necrotic regions within the tissues (0.1 to 2.7 dpm/mm2). Normal cells within the tissue sections did not have detectable levels of VEGF mRNA. For comparison, tumor levels of c-myc (4 to 46 dpm/mm2) and glyceraldehyde-3-phosphate dehydrogenase mRNAs (48 to 214 dpm/mm2) were measured. The mRNAs for both of these genes were more broadly expressed across the tissue sections. The hybridization pattern for VEGF mRNAs was consistent with hypoxia-induced VEGF mRNA steady-state levels and supports the hypothesis that oxidative stress regulates VEGF expression in breast tumors.
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PMID:Quantitation of vascular endothelial growth factor mRNA levels in human breast tumors and metastatic lymph nodes. 920 8

Growth of trophoblast tissue in early pregnancy is rapid and accomplished in an unusually hypoxic environment. Hypoxia has been reported to upregulate mRNA production of vascular endothelial growth factor (VEGF), and VEGF receptors have been found on trophoblast cells. These observations suggest that VEGF may have an important role in early placentation. This study examines the influence of hypoxia on both the production of the VEGF message and protein and on the production of human chorionic gonadotrophin (hCG) protein by the cell lines JEG, JAr and BeWo. Cells were grown under normoxic and hypoxic conditions for 72 h. The average oxygen tension in the culture media of the hypoxic cultures (6-7 kPa) was significantly less than in the normoxic cultures (19-21 kPa). RNA was extracted and message for VEGF(121), VEGF(165) and VEGF(189) found in all cell lines by reverse transcription and the polymerase chain reaction (RT-PCR). These messages were upregulated by hypoxia; findings confirmed by competitive PCR for VEGF and expression of the house keeping gene GAPDH. hCG and VEGF were measured by immunoassay. Hypoxia resulted in an increase in VEGF production (P<0.05) but had inconsistent effects on hCG production. In some experiments the absolute concentrations of hCG and VEGF in the culture media were noted to be significantly correlated (r>0.5, P<0.05). In addition to its role in angiogenesis, VEGF may have direct effects on trophoblast cells encouraging proliferation and invasion. These effects may be regulated in part through oxygen supply and hCG.
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PMID:Influence of hypoxia on vascular endothelial growth factor and chorionic gonadotrophin production in the trophoblast-derived cell lines: JEG, JAr and BeWo. 925 Jul 9

Increased microvascular permeability, which occurs in conditions such as the adult respiratory distress syndrome and diabetes mellitus, is related to physicochemical alterations in the microvascular barrier. We postulate that, in part, capillary pericytes affect microvascular permeability via production of a vasoactive cytokine, viz, vascular endothelial growth factor (VEGF), also known as vascular permeability factor. The goal of the present study was to evaluate the effects of phorbol myristate acetate (PMA), a substance known to produce nonhydrostatic pulmonary edema in intact animals, on VEGF gene expression in pericyte cultures. Microvascular pericytes were isolated from bovine retinas using magnetic microspheres coated with 3G5 monoclonal antibody. Pericyte identity was confirmed both morphologically and by immunostaining for alpha-smooth muscle actin and 3G5 ganglioside. The cultured pericytes were stimulated with N(omega)-nitro-L-arginine methyl ester (L-NAME, 1 x 10(-4) mmol/L), angiotensin II (1 x 10(-6) mmol/L), and PMA (5 x 10(-8) mmol/L), selected because of their ability to upregulate VEGF mRNA expressions in other cell types. Northern blot analysis was performed using [32P]dCTP labeled human VEGF cDNA (Genentech). Lane-loading differences were normalized using mouse GAPDH control cDNA probe. VEGF mRNA expression was upregulated by PMA (10(-9) to 10(-6) mol/L) in a dose-dependent manner, whereas neither L-NAME nor angiotensin II affected VEGF mRNA expression in pericytes. These results support the hypothesis that pericytes increase permeability of the endothelial barrier through increased VEGF production.
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PMID:Vascular endothelial growth factor mRNA in pericytes is upregulated by phorbol myristate acetate. 945 54

Expression of vascular endothelial growth factor (VEGF), an angiogenic factor and endothelial cell-specific mitogen, is induced by hypoxia in various cell lines as well as in solid tumors. In this study, we report that cell density has a profound effect on the expression of VEGF in human glioblastoma cells (U87) and human fibrosarcoma cells (HT1080), an effect that is independent of hypoxia. Northern blot analysis revealed that VEGF mRNA levels were four- to eightfold higher in cells seeded at high density compared to cells seeded at low density. This upregulation of VEGF message in response to seeding at high density was not seen with other mRNAs such as those for TGF-beta1 or GAPDH. Conditioned medium switch experiments between sparse and dense cells suggested that soluble factor(s) may not account for the observed changes in VEGF expression. Incubation with genistein, a protein tyrosine kinase inhibitor, for 3 h following seeding resulted in the reduction of the VEGF mRNA levels in highly confluent cultures but not in sparse cultures. To identify protein tyrosine kinases involved in the upregulation of the steady-state levels of VEGF mRNA in highly dense cultures, we analyzed the phosphorylation state of the c-src tyrosine kinase, in high versus low confluency cultures of U87 and HT1080 cells. Interestingly, an increased phosphorylation at Tyr416 of c-src was noted in high compared to low confluency, suggesting the activation of c-src in highly confluent cultures. Because extracellular signal-regulated kinases (ERKs) such as MAP kinase have been shown to be activated by extracellular stimuli and act downstream of c-src, we examined their possible involvement in this process. We found that the tyrosine phosphorylation level of MAP kinase is higher in dense compared to sparse cultures and, moreover, 6-thioguanine (6-TG), a potent inhibitor of ERKs, reduced VEGF mRNA levels in high but not low confluency. Furthermore, reintroduction of wild-type, but not mutant, von Hippel-Lindau (VHL) gene product in 786-O cells (a renal carcinoma cell line) specifically abrogated the induction of VEGF mRNA due to high cell density. Taken together, these data suggest that VEGF gene expression is regulated by cell density, and the protooncogene c-src and the tumor-suppressor VHL are modulators of this regulation.
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PMID:High cell density induces vascular endothelial growth factor expression via protein tyrosine phosphorylation. 957 97

It has been suggested that human iris pigment epithelial (IPE) cells isolated from iridectomized tissue could be used as autologous cells for transplantation into the subretinal space in diseases with dysfunctional retinal pigment epithelium (RPE). RPE cells synthesize a number of cytokines and their receptors which are important for its proper function. Nearly nothing is known about the capacity of IPE to synthesize cytokines or responding to them. To compare the mRNA expression of 36 cytokines or their receptors in cultured adult IPE cells and RPE cells we used semi-quantitative reverse transcription polymerase chain reactions (RT-PCR). Included in our assay were cytokines with known expression in RPE to get a broad basis for comparing IPE cells: basic fibroblast growth factor (bFGF or FGF-2), and one of its receptor (FGFR-1), epidermal growth factor (EGF), and its receptor EGF-R, transforming growth factor beta(TGFbeta), and its type III receptor TGFbeta-R3, the platelet-derived growth factors and receptors (PDGF A, PDGF B, PDGF-Ralpha, PDGF-Rbeta), tumor necrosis factor alpha(TNFalpha), and two receptors TNF-R1 and TNF-R2, insulin (INS) with receptor INS-R, insulin-like growth factors (IGF1, IGF2), and receptors (IGF1-R, IGF2-R), vascular endothelial growth factor (VEGF), and two receptors (VEGF-R1 or FLT-1 and VEGF-R2 or FLK-1), the receptor for VEGF-C: VEGF-R3 or FLK-4, interleukin 6 (IL6), and its receptor (IL6-R), nerve growth factor (NGF), interleukin 1alpha(IL1alpha), and a receptor (IL1-R). In addition, cytokines or their receptors not known to be expressed in RPE were included to widen our picture of cytokine gene expression in the eye: stem cell factor (SCF), its receptor (SCF-R), low-affinity nerve growth factor receptor p75 (p75(NGF-R), ciliary neutrothropic factor (CNTF), and its receptor (CNTF-R), glycoprotein 130 interleukin 6 transducer (gp130 (IL6-SD), leukemia inhibitory factor (LIF), and its receptor (LIF-R). Semi-quantitative expression data were obtained using series of fivefold dilutions of each cDNA and a fixed number of PCR cycles. The expression of RPE 65, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and beta2-microglobulin (B2MG) was used as a control for cellular origin, RNA quality and PCR conditions. With the exception of insulin and tumor necrosis factor alphaall other cytokines analysed and their receptors were expressed in both IPE and RPE cells, even though the levels varied. No qualitative or quantitative difference were observed in the mRNA expression level of 34 (94%) of the cytokines or receptors between IPE and RPE. In contrast, the mRNA expression level of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor 2 [VEGF-RS (FLK-1)] was lower in IPE than in RPE cells. As an increased expression of VEGF in the RPE in maculae with age-related macular disease could be involved in its pathogenesis, a decreased expression of angiogenic growth factors in IPE cells could possibly be beneficial for the therapy of age-related maculopathy if indeed other tasks of non-functional RPE cells could be performed by IPE cells. The similarity of the mRNA expression pattern in 94% of the cytokines analyzed supports the assumption that IPE cells potentially can perform functions of RPE cells in the appropriate environment.
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PMID:The mRNA expression of cytokines and their receptors in cultured iris pigment epithelial cells: a comparison with retinal pigment epithelial cells. 973 90

Angiogenic factors such as vascular endothelial growth factor (VEGF) may be involved in neovascularization of malignant tumors. Our aim was to determine whether there is an increased VEGF mRNA expression in liver from patients with HCC and premalignant hepatitis C virus (HCV) with differing severity of inflammation. VEGF mRNA (VEGF165, VEGF189) was detected by reverse transcription and semi-quantitative polymerase chain reaction (RT-PCR) amplification in all liver samples. There was no difference in VEGF mRNA expression ratios (corrected for glyceraldehyde-3-phosphate dehydrogenase) among three groups: steatohepatitis, as a non-malignant non-viral control, 1. 05+/-0.35, n=8; chronic hepatitis C, 0.86+/-0.27, n=18; hepatocellular carcinoma, 1.06+/-0.43, n=10. VEGF mRNA expression was independent of the severity of HCV inflammation estimated by the histological activity index: low HAI (</=4, n=8) vs. high HAI (>/=10, n=10), 0.93+/-0.31 vs. 0.81+/-0.24, p=ns. There was no significant difference in mean VEGF expression between HCC tumor (1.06+/- 0.43) and adjacent tissue (0. 85+/-0.42) although the tumors tended to have higher expression than adjacent non-malignant tissues. In conclusion, all liver samples of steatohepatitis, chronic HCV infection and HCC expressed VEGF mRNA, VEGF mRNA may be uniformly expressed in liver tissue, the level of expression is probably not related to virus infection or the severity of inflammation. Other angiogenic or angiostatic factors might be more involved in angiogenesis in HCC.
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PMID:Vascular endothelial growth factor/vascular permeability factor mRNA expression in patients with chronic hepatitis C and hepatocellular carcinoma. 991 13

We studied vascular endothelial growth factor (VEGF) mRNA synthesis by peripheral blood mononuclear cells (PBMCs) in 30 patients with acute myocardial infarction (AMI) and 20 healthy individuals. PBMCs were isolated from all patients on days 3 and 14 after the onset of aMI, and from all of control individuals. To prepare samples containing identical amounts of GAPDH cDNA, competitive PCR was performed by co-amplifying serial dilutions of GAPDH mutant templates. Next, to measure VEGF cDNA quantitatively in the samples containing identical amounts of GAPDH, we also used competitive PCR by co-amplifying mutant templates of VEGF. The serum VEGF concentrations on day 14 in patients with aMI were measured by an ELISA method. Higher levels of VEGF mRNA in PBMCs were present on day 14 than either on day 3 or in the control group. Serum VEGF concentrations correlated with the VEGF mRNA levels of PBMCs on day 14. Peak serum CK levels correlated well with VEGF mRNA levels of PBMCs on day 14. The present findings suggest that PBMCs may be one of the candidates responsible for elevated circulatory VEGF protein following aMI. In addition, VEGF mRNA may be overexpressed in PBMCs in response to cardiac muscle damage.
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PMID:Vascular endothelial growth factor mRNA synthesis by peripheral blood mononuclear cells in patients with acute myocardial infarction. 1169 Jun 65


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