Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The lipoxygenase (LO) pathway has been implicated in leading to accelerated atherosclerosis. However, the precise type of LO present in unstimulated human aortic smooth muscle cells (HSMC), endothelial cells (HAEC), and monocytes (MO) is not clear. In this study, we used a specific reverse-transcriptase polymerase chain reaction (RT-PCR) method to analyze the type of LO mRNA expressed in normal HSMC, HAEC, and MO. In all three cell types, a 333-base-pair band was seen when primers and probes specific for the leukocyte type of 12-LO were used, suggesting that a leukocyte type of 12-LO is expressed in these cell types. Western immunoblotting analysis in cultured HSMC, HAEC, and MO using a polyclonal peptide antibody to the leukocyte type of 12-LO showed a specific 72-kD band that is identical to the molecular weight of the leukocyte type of 12-LO. These results indicate that a leukocyte type of 12-LO RNA and protein are expressed in HSMC, HAEC, and MO. Further, angiotensin II upregulates 12-LO activity and expression in HSMC, supporting a role for this 12-LO pathway in human vascular disease.
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PMID:A leukocyte type of 12-lipoxygenase is expressed in human vascular and mononuclear cells. Evidence for upregulation by angiotensin II. 760 Jan 27

Severe methylenetetrahydrofolate reductase (MTHFR) deficiency is an inborn error of folate metabolism, and is inherited as an autosomal recessive trait. MTHFR is a key enzyme in folate-dependent remethylation of homocysteine, and reduces 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. Patients with this severe enzymatic deficiency are biochemically characterised by homocystinuria and hypomethioninaemia, and may suffer from neurological abnormalities, mental retardation and premature vascular disease. Here we report the molecular basis of severe MTHFR deficiency in four unrelated families from Turkish/Greek ancestry. By use of reverse-transcriptase (RT)-PCR, subsequently followed by direct sequencing analysis, we were able to identify four novel mutations in the MTHFR gene: two missense (983A-->G; 1027T-->G) and two nonsense (1084C-->T; 1711C-->T) mutations. Furthermore, a splice variant containing a premature termination codon, was observed in one patient, probably as a secondary effect of the 1027T-->G missense mutation. The ongoing identification and characterisation of mutations in the MTHFR gene will provide further insight into the heterogeneity of the clinical phenotype in severe MTHFR deficiency.
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PMID:Identification of four novel mutations in severe methylenetetrahydrofolate reductase deficiency. 978 Oct 30

There is a striking gender difference in atherosclerotic vascular disease. For decades, testosterone was considered detrimental to the cardiovascular system. Recent studies, however, have presented some alternative results. The aim of this study was to evaluate the effect of testosterone, using physiological and supraphysiological concentrations, on antigen and mRNA levels of tissue plasminogen activator (tPA), plasminogen activator inhibitor type 1 (PAI-1), and tissue factor pathway inhibitor (TFPI) released by human umbilical vein endothelial cells and to investigate the cellular mechanism. Cells within 2-3 passages were cultured in 25 cm(2) flasks or plated onto 96-well plates with a density of about 1 x 10(5) cells/mL as recommended. The cells were incubated in the presence or absence of testosterone (3, 30, 3 x 10(3), 3 x 10(4) nmol/L) for 48 h. Levels of tPA, PAI-1, and TFPI antigen were assayed with ELISA kits. Reverse transcriptase PCR was carried out to detect tPA, PAI-1, and TFPI mRNA levels. Cells were incubated in androgen-receptor antagonist (flutamide 10 micromol/L) or aromatase inhibitor (aminoglutethimide 50 micromol/L) for 3 h, and then the experiments were repeated. Testosterone at a physiologic concentration (30 nmol/L) increased the antigen levels of tPA and TFPI significantly (P < 0.05). However, tPA and TFPI levels were markedly reduced (P < 0.05) at a larger dose (3 x 10(4) nmol/L). On the other hand, PAI-1 antigen levels decreased significantly at the testosterone concentrations ranging from 3 to 3 x 10(4) nmol/L (P < 0.05). The change in the levels of tPA and TFPI were reflected in the corresponding change in mRNA levels. Flutamide attenuated the effect of testosterone at physiological concentration (30 nmol/L). The results demonstrated that testosterone at physiological concentrations may have a beneficial influence on the haemostatic system through enhancement of anticoagulant activity, resulting from stimulation of TFPI and tPA expression and inhibition of PAI-1 secretion by the endothelium.
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PMID:Physiological testosterone stimulates tissue plasminogen activator and tissue factor pathway inhibitor and inhibits plasminogen activator inhibitor type 1 release in endothelial cells. 1753 6