Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of anoxia and reoxygenation on the synthesis and secretion of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) was studied in primary cultures of human umbilical vein endothelial cells. Sublethal anoxia, determined by trypan blue dye exclusion and lactate dehydrogenase release, was produced by cell culture under a 95% N2, 5% CO2 atmosphere for 2-24 h and was followed by reoxygenation with 95% air, 5% CO2 for 24 or 48 h. Anoxia did not alter the levels of mRNA for t-PA or PAI-1 in the cells or the secretion of t-PA or PAI-1 into the medium. At 24 h, t-PA secreted into conditioned medium was 7.0 +/- 1.4 ng/2 x 10(6) cells (n = 9) and PAI-1 was 300 +/- 13 IU/2 x 10(6) cells (n = 9), whereas the content of t-PA mRNA was 2.2 pg/micrograms of RNA and PAI-1 mRNA was 180 pg/micrograms of RNA. During reoxygenation, however, t-PA antigen and PAI-1 activity as well as mRNA for PAI-1 decreased proportionally to the duration of anoxia, to reach 27 +/- 1.0, 49 +/- 2.0, and 47 +/- 14% of control values, respectively, within 24 h of anoxia. t-PA mRNA also decreased significantly during reoxygenation following anoxia, but the extent could not be accurately quantitated. Addition, during anoxia, of a 200 micrograms/ml concentration of the superoxide anion radical scavenger superoxide dismutase or of a 5 mM concentration of the iron chelator deferoxamine mesylate prevented the subsequent decrease of t-PA antigen during reoxygenation; addition of these compounds during reoxygenation had no effect. Superoxide dismutase, but not deferoxamine mesylate, when added during anoxia prevented the subsequent decrease in PAI-1 activity. These studies suggest that the marked alteration of endothelial cell fibrinolysis during anoxia followed by reoxygenation is most likely mediated by a mechanism dependent on oxygen radicals. Impaired endothelial cell fibrinolysis may contribute to the pathophysiology of ischemia/reperfusion injury.
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PMID:Oxygen radicals generated during anoxia followed by reoxygenation reduce the synthesis of tissue-type plasminogen activator and plasminogen activator inhibitor-1 in human endothelial cell culture. 212 75

Biochemical markers of early changes that are characteristic for diabetic microangiopathy are not completely understood. We investigated activities of serum N-acetyl-beta-glucosaminidase (NAG), tissue plasminogen activator and erythrocyte superoxide dismutase in well defined groups of type 1 diabetic patients. Patients were selected on the basis of 4 year follow-up observation. Forty-two type 1 diabetic patients were subdivided into those without retinopathy (n = 13) throughout the study, those with newly developed or worsened retinopathy (n = 12) during 4 years and those with retinopathy already established at the beginning of the study and without evidence of its progression (n = 17). All diabetic patients had albustix-negative urine. A significant increase of the mean serum NAG activity during 4 years was found only in patients without retinopathy (P < 0.01) whereas no changes of the altered enzyme activities were present in patients with developing and established retinopathy. The mean activity of tissue plasminogen activator was elevated in all groups of diabetic patients compared with healthy subjects (P < 0.001). A significant positive correlation was found between plasminogen activator and serum NAG (r = 0.51, P < 0.01). Erythrocyte superoxide dismutase was higher in diabetic patients than in healthy persons (P < 0.01) but no differences were observed between the patients with or without retinopathy. Superoxide dismutase positively correlated with NAG (r = 0.57, P < 0.01). We conclude that early functional changes precede a morphological development of diabetic retinopathy as was evident from the altered enzyme activities.
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PMID:Early changes of serum N-acetyl-beta-glucosaminidase, tissue plasminogen activator and erythrocyte superoxide dismutase in relation to retinopathy in type 1 diabetes mellitus. 798 55

New therapies of cerebral vasospasm aim to prevent the effects of subarachnoid haemorrhage. These effects result in red blood cell haemolysis and release of oxyhaemoglobin, free radicals formation and lipid peroxidations, imbalance in endothelial modulation of vasomotor tone and activation of the complement system. Low doses of fibrinolytic agents administered intrathecally accelerate the fibrinolysis of the clot and reduce the oxyhaemoglobin release. The tissue-type plasminogen activator has proven to be effective in preventing vasospasm, but the modalities of this therapy remain to be defined. Free radical reactions may be inhibited by free radical scavengers and inhibitors of lipid peroxidations. Tirilazad is a potent inhibitor of lipid peroxidations, which improves the patients' outcome and has gone to Phase III human trials. Superoxide dismutase and tropolone derivatives are currently evaluated in animal models. Vasomotor tone can be modified in experimental models either by blocking endothelin receptors (BQ-123), or by facilitating the release and enhancing the effect of nitric oxide using protein kinase C inhibitors, drugs that increase intracellular calcium (cyclopiazonic acid, LP-805) and free radicals scavengers (superoxide dismutase). These possibilities are being investigated. Finally, preliminary studies have demonstrated the efficacy of FUT-175, an inhibitor of the complement system, in the prevention of vasospasm. In the next years, these new therapies have to be validated by prospective and randomized clinical trials to propose guidelines for the management of patients at risk of cerebral vasospasm after aneurysmal rupture.
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PMID:[Pharmacological therapeutic prospects of cerebral vasospasm]. 875 98