Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.2.1.13 (glyceraldehyde-3-phosphate dehydrogenase)
 6,511 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Placental development requires adequate and organized interaction of vascular growth factors and their receptors, including vascular endothelial growth factor (VEGF) and placental growth factor (PlGF). Both VEGF and PlGF, acting through the tyrosine kinase receptors VEGFR-1 and VEGFR-2, have been implicated in playing a role in ovine placental vascular development. The present studies describe the placental expression of components of the VEGF family at two maturational time points (55 and 90 days post coitus, dpc) in a hyperthermic-induced ovine model of placental insufficiency-intrauterine growth restriction (PI-IUGR). Both caruncular and cotyledonary VEGF and PlGF mRNA concentration increased with gestational age (P< 0.05), whereas only cotyledonary VEGF and PlGF protein concentration increased over gestation (P< 0.002). At 55 dpc, VEGF mRNA concentration was elevated in hyperthermic (HT) ewes, compared to control thermoneutral (TN) animals (TN; 0.52+/-0.08 vs HT; 1.27+/-0.17 VEGF/GAPDH, P< 0.001). At 90 dpc, expression of PlGF and VEGF mRNA was not altered by the HT treatment. Both TN cotyledonary VEGFR-1 and VEGFR-2 mRNA expression levels rose significantly over the period studied (P< 0.05 and P< 0.01 respectively). Receptor mRNA concentration in HT cotyledonary tissue was significantly reduced at 90 dpc (VEGFR-1; TN 0.21+/-0.02 vs HT 0.11+/-0.01 VEGFR-1/actin, P< 0.05, VEGFR-2; TN 0.18+/-0.05 vs HT 0.07+/-0.01 VEGFR-2/actin, P< 0.01). Soluble VEGFR-1 (sVEGFR-1) mRNA was not detected in these tissues. These alterations in growth factor and growth factor receptor mRNA expression, as a result of environmental heat stress early in placental development, could impair normal placental vascular development. Furthermore, alterations in VEGF, VEGFR-1 and VEGFR-2 mRNA expression, during the period of maximal placental growth, may contribute to the development of placental insufficiency, and ultimately intrauterine growth restriction.
 ...
PMID:Placental expression of VEGF, PlGF and their receptors in a model of placental insufficiency-intrauterine growth restriction (PI-IUGR). 1194 79

Angiogenesis is implicated in a variety of human pathologies and may also play a role in the progression of heart failure. We have studied the expression of members of the vascular endothelial growth factor (VEGF) and the angiopoietin families and their receptors in mice lacking the mitochondrial transcription factor A. These mice lack functional respiratory chain activity in their myocytes and develop dilated cardiomyopathy (DCM) postnatally. We studied the hearts of the knockout mice by in situ hybridization, Western blotting analysis, and immunohistochemistry. VEGF-A mRNA and protein levels were elevated in the myocardium of the knockouts. Levels of the hypoxia inducible transcription factor 1 alpha (HIF1 alpha) and of glyceraldehyde-3-phosphate dehydrogenase transcripts were also increased, whereas those of angiopoietin-1 and -2 were reduced. Despite the striking upregulation of VEGF-A, there was no increase in capillary density in the knockout hearts. This study suggests that a disturbance in angiogenesis may contribute to the pathogenesis of DCM.
 ...
PMID:Upregulation of VEGF-A without angiogenesis in a mouse model of dilated cardiomyopathy caused by mitochondrial dysfunction. 1207 Feb 72

Careful normalization is essential when using quantitative reverse transcription polymerase chain reaction assays to compare mRNA levels between biopsies from different individuals or cells undergoing different treatment. Generally this involves the use of internal controls, such as mRNA specified by a housekeeping gene, ribosomal RNA (rRNA), or accurately quantitated total RNA. The aim of this study was to compare these methods and determine which one can provide the most accurate and biologically relevant quantitative results. Our results show significant variation in the expression levels of 10 commonly used housekeeping genes and 18S rRNA, both between individuals and between biopsies taken from the same patient. Furthermore, in 23 breast cancers samples mRNA and protein levels of a regulated gene, vascular endothelial growth factor (VEGF), correlated only when normalized to total RNA, as did microvessel density. Finally, mRNA levels of VEGF and the most popular housekeeping gene, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), were significantly correlated in the colon. Our results suggest that the use of internal standards comprising single housekeeping genes or rRNA is inappropriate for studies involving tissue biopsies.
 ...
PMID:Quantitative real-time reverse transcription polymerase chain reaction: normalization to rRNA or single housekeeping genes is inappropriate for human tissue biopsies. 1241 63

Osteogenesis and angiogenesis occur in a coordinated manner in skeletal tissue, so that impaired angiogenesis is associated with decreased bone formation in aged subjects. However, the interaction between bone endothelium and osteoblastic cells is poorly understood. Parathyroid hormone-related protein (PTHrP), a bone factor which modulates osteoblastic cell growth and/or differentiation, stimulates vascular endothelial growth factor (VEGF), a potent angiogenic factor, in primary cultures of human osteoblastic (hOB) cells. In the present study, we examined the age-related changes of both factors in these cells. Human OB cells were isolated from trabecular bone samples from knee or hip explants obtained from 45 osteoarthritic patients: 12 <60 years (21-59 years), 5 women and 7 men, and 33 >60 years (61-82 years), 20 women and 13 men. Cell total RNA was isolated, and mRNA analysis was performed by reverse transcription-polymerase chain reaction. Relative ratios of amplified products with respect to glyceraldehyde-3-phosphate dehydrogenase were then calculated. PTHrP and VEGF were measured in the cell-conditioned medium, after stimulation with (or without) 10 nM 1,25(OH)(2)D(3) for 72 h, using specific immunoradiometric assay and a competitive immunoassay, respectively. A positive correlation was found between PTHrP and VEGF (both mRNA and secreted protein), and also between PTHrP mRNA and the secreted protein levels, in these cells. PTHrP, both mRNA and protein secretion levels, and VEGF secreted values were higher in knee hOB cells than in hip hOB cells only in the younger group. In addition, a decrease in the secreted levels of these factors occurs with aging only in hOB cells from knee. Treatment with 10 nM 1,25(OH)(2)D(3) induced a lower inhibitory response of PTHrP secretion, and a higher stimulatory response of secreted VEGF, in hOB cells with age. These findings indicate that age-related bone loss in humans is associated with a decrease in the osteoblastic secretion of both PTHrP and VEGF in the knee, a predominantly trabecular bone. These data might provide a rationale to explain the impaired angiogenesis associated with trabecular bone loss in aging.
 ...
PMID:Age-related changes in parathyroid hormone-related protein and vascular endothelial growth factor in human osteoblastic cells. 1241 34

The recent development of the laser microdissection (LMD) technique enables one to target particular tissues or cells for gene or protein analyses. The purpose of this study was to detect local mRNA expression of vascular endothelial growth factor (VEGF) and its receptor, flk-1, in the glomeruli of normal rat kidneys using the LMD system. Frozen sections of the kidney of 8-week-old male Wistar rats were made. The glomeruli were dissected from the frozen sections with the LMD system, and total RNA was extracted from 200 glomeruli in each kidney. Reverse-transcription polymerase chain reaction (RT-PCR) revealed the local mRNA expression of three isoforms of VEGF, flk-1 and GAPDH in the glomeruli. Moreover, the real-time PCR was performed to evaluate the experimental condition for quantification of VEGF and flk-1 mRNA expression using this system, and the results showed that at least 10 glomeruli might be needed for quantifying local VEGF mRNA expression. However, cDNA from 200 glomeruli was not enough for quantitative evaluation of flk-1 mRNA with this system. These results demonstrate the reproducibility of the analysis of mRNA expression in the renal glomeruli using the LMD system and also suggest that the application of the LMD technique will provide information to further our understanding of the mechanisms involved in kidney diseases.
 ...
PMID:Detection of gene expression of vascular endothelial growth factor and flk-1 in the renal glomeruli of the normal rat kidney using the laser microdissection system. 1259 67

ANG II regulates growth factor expression in the kidney. We investigated whether ANG II regulated vascular endothelial growth factor (VEGF) synthesis in proximal tubular epithelial (MCT) cells. ANG II (1 nM) increased VEGF protein expression within 5 min, the effect lasting for 30 min. There was no change in VEGF mRNA levels or mRNA stability, and transcription inhibitors did not affect ANG II-induced VEGF expression. Regulation of VEGF translation was investigated. Polyribosomal analysis revealed selective enrichment of heavy ribosomes (polysomes) with VEGF mRNA transcripts compared with light ribosomes in ANG II-treated cells, although distribution of GAPDH was unaltered. In vitro translation of total RNA from polysomal fractions showed selective increase in VEGF protein synthesis in ANG II-treated cells. Preincubation with LY-294002, a PI 3-kinase inhibitor, or expression of dominant-negative Akt prevented ANG II-stimulated increase in VEGF translation. ANG II increased phosphorylation of eukaryotic initiation factor 4E and its binding protein 4E-BP1, critical events that regulate the initiation phase of protein translation. ANG II failed to increase VEGF mRNA translation in cells stably expressing the phosphorylation mutant of 4E-BP1. Our data illustrate that a rapid increase in VEGF protein expression by ANG II is regulated at the initiation phase of translation of VEGF mRNA in renal epithelial cells. Regulation of VEGF translation by ANG II represents a novel pathway of renal response to injury.
 ...
PMID:Translational regulation of vascular endothelial growth factor expression in renal epithelial cells by angiotensin II. 1557 20

To establish reproductive biological techniques in mammals, it is important to understand the growth environment of the embryo. Oviduct epithelial cells are in close proximity to the embryo during pre-implantation development. We, therefore, established an immortalized oviduct epithelial cell line from the cynomolgus monkey, evaluated the usefulness of these cells as feeder cells for embryo culture, and investigated the gene expression of several growth factors and cytokines in the cells. The immortalized cells were positive for the anti-cytokeratin antibody, as determined by immunocytochemistry, indicating that they are epithelial. They also expressed oviductin, which is specific to oviduct epithelial cells, glyceraldehyde-3-phosphate dehydrogenase (control), leukemia inhibitory factor, vascular endothelial growth factor, epidermal growth factor, insulin-like growth factor 1, transforming growth factor beta-2, and interleukin 4. Mouse embryo development was improved when the immortalized cells were used as feeder cells. This cell line is also useful for studying the factors secreted by oviduct epithelial cells.
 ...
PMID:Characterization of an immortalized oviduct cell line from the cynomolgus monkey (Macaca fascicularis). 1586 Jan 12

Bone morphogenetic proteins (BMPs) are known to promote osteogenesis, and clinical trials are currently underway evaluating the ability of certain BMPs to promote bone graft and fracture healing. To observe the mechanism of osteoinductive and bone formation, 100 microg of bovine BMP was tested during osteogenic differentiation of rat bone marrow stromal cells (MSCs) and C2C12 line culture for 14 and 28 days. We examined alkaline phosphatase (ALP) by assay, immunohistochemical studies for bone matrix proteins, and mRNA expression of bone matrix proteins and osteoblast-related analysis by reverse-transcription polymerase chain reaction. ALP activity in MSC cultures was elevated by bovine BMP by two to fivefold (P < 0.05-0.001). DNA and protein content increased over 14 days. BMP significantly increased the mRNA expression of type I collagen, ALP, osterix, osteocalcin, osteopontin, vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF)-A, and parathyroid hormone receptor time dependently during the osteoblastic differentiation. There was no markedly enhanced mRNA expression of bone sialoprotein (BSP) and glyceraldehyde-3-phosphate dehydrogenase compared with that of control. Immunohistochemical results also showed BMP increased immunoreactive positivity of type I collagen, osteocalcin, osteonectin, osteopontin, and BSP during the C2C12 differentiation. These data indicated that BMP enhances our ability to stimulate the differentiation of osteoblast-like cells and increases osteoinductivity, bone matrix protein formation and mineralization, angiogenesis, and chondrogenesis during osteoblast progenitor cell differentiation in vitro and that the role of chondrogenic is weak.
 ...
PMID:Role of bovine bone morphogenetic proteins in bone matrix protein and osteoblast-related gene expression during rat bone marrow stromal cell differentiation. 1632 48

Eukaryotic initiation factor 4E (eIF4E) binds to the 5' m(7)G cap of mRNAs and is a focal point of regulation of initiation of mRNA translation. High levels of expression of eIF4E in many epithelial cancers, including breast, head and neck, colon, and bladder, correlate with increased tissue invasion and metastasis. To further examine the role of eIF4E in the biology of cancer cells, variants of eIF4E with impaired 5' cap binding function were expressed in MDA-MB-435 carcinoma cells. Cell lines overexpressing variants of eIF4E had impaired growth properties and exhibited a different morphology compared to cells expressing similar amounts of exogenous wild-type eIF4E or control cells. Cells expressing variant eIF4E did not form foci in culture and produced smaller colonies in soft agar compared to cells expressing wild-type eIF4E. In addition, analysis of polyribosomes for vascular endothelial growth factor (VEGF) mRNA demonstrated a shift from translationally active to inactive fractions in variant eIF4E cells, while GAPDH mRNA did not. The long G-C rich 5' untranslated region of VEGF mRNA is a feature of other mRNAs encoding growth regulating proteins that are predicted to have their translation enhanced by increases in eIF4E; whereas mRNA with shorter and less structured 5' UTRs, like that of GAPDH, are predicted to be largely unaffected. These data suggest that targeting the 5' cap-binding domain of eIF4E may be a viable option to slow cancer cell growth and alter the malignant phenotype.
 ...
PMID:Eukaryotic initiation factor 4E variants alter the morphology, proliferation, and colony-formation properties of MDA-MB-435 cancer cells. 1709 71

In bladder outlet obstruction (BOO), mechanical stress and ischemia/hypoxia are implicated in structural and functional alterations of the urinary bladder. Because mechanical stress and hypoxia may trigger endoplasmic reticulum (ER) stress, we examined involvement of ER stress in the damage of the bladder caused by BOO. An experimental model of BOO was established in rats by complete ligature of the urethra for 24 h, and bladders were subjected to northern blot analysis and assessment of apoptosis. Isolated urinary bladders and bladder-derived smooth muscle cells (BSMCs) were also exposed to mechanical strain and hypoxia and used for analyses. To examine involvement of ER stress in the damage of the bladder, the effects of a chemical chaperone 4-phenylbutyrate (4-PBA) were evaluated in vitro and in vivo. Outlet obstruction for 24 h induced expression of ER stress markers, GRP78 and CCAAT/enhancer-binding protein-homologous protein (CHOP), in the bladder. It was associated with induction of markers for mechanical stress (cyclooxygenases 2) and hypoxia (vascular endothelial growth factor and glyceraldehyde-3-phosphate dehydrogenase). When isolated bladders and BSMCs were subjected to mechanical strain, induction of GRP78 and CHOP was not observed. In contrast, when BSMCs were exposed to hypoxic stress caused by CoCl2 or thenoyltrifluoroacetone (TTFA), substantial upregulation of GRP78 and CHOP was observed, suggesting involvement of hypoxia in the induction of ER stress. In the bladder subjected to BOO, the number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive cells increased in the epithelial cells and BSMCs. Similarly, treatment with TTFA or CoCl2 induced apoptosis of BSMCs, and 4-PBA significantly attenuated ER stress and apoptosis triggered by these agents. Furthermore, in vivo administration with 4-PBA significantly reduced apoptosis in the bladder subjected to BOO. These results suggested that outlet obstruction caused ER stress via hypoxic stress in the bladder and that hypoxia-triggered ER stress may be involved in the induction of apoptosis in BOO.
 ...
PMID:Involvement of hypoxia-triggered endoplasmic reticulum stress in outlet obstruction-induced apoptosis in the urinary bladder. 1834 81


<< Previous 1 2 3 4 Next >>