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)

Three compounds with anti-inflammatory activity were isolated from Schinus molle fruits. Two of the compounds were identified as 3- epi-isomasticadienolalic acid ( 1), isomasticadienonalic acid ( 2) and chamaejasmin ( 3). Triterpenes 1 and 2, and biflavanone 3 were tested on two models of mice paw inflammation: one of acute inflammation, induced by subcutaneous injection of either phospholipase A (2) (PLA (2)) or carrageenan in the paws of mice, and one of chronic inflammation in the form of eczema, provoked by repeated administration of TPA to the ears of mice. On the PLA (2)-induced mouse paw oedema, only 2 was active (30 mg/kg, 66 % inhibition at 60 min), whereas all compounds reduced the chronic model of inflammation (48 to 26 % of swelling reduction), but only triterpenes reduced the leukocyte infiltration, measured as tissue peroxidase activity. In the case of the carrageenan-induced mouse paw oedema, only 3 led to a reduction of the swelling 3 h after challenge (50 mg/kg, 46 % oedema inhibition). In addition, 3 inhibited the LTB (4) production in rat peritoneal polymorphonuclear leukocytes with an IC (50) value of 29.8 microM, while triterpenes showed toxicity against cells at 100 microM.
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PMID:Isolation of two triterpenoids and a biflavanone with anti-Inflammatory activity from Schinus molle fruits. 1464 90

Neuroserpin is a member of the serine proteinase inhibitor (serpin) gene family that reacts preferentially with tissue-type plasminogen activator (tPA) and is primarily localized to neurons in regions of the brain where tPA is also found. Outside of the central nervous system (CNS) tPA is predominantly found in the blood where its primary function is as a thrombolytic enzyme. However, tPA is also expressed within the CNS where it has a very different function, promoting events associated not only with synaptic plasticity but also with cell death in a number of settings, such as cerebral ischemia and seizures. Neuroserpin is released from neurons in response to neuronal depolarization and plays an important role in the development of synaptic plasticity. Following the onset of cerebral ischemia there is an increase in both tPA activity and neuroserpin expression in the area surrounding the necrotic core (ischemic penumbra), and treatment with neuroserpin following ischemic stroke or overexpression of the neuroserpin gene results in a significant decrease in the volume of the ischemic area as well as in the number of apoptotic cells. TPA activity and neuroserpin expression are also increased in specific areas of the brain by seizures, and treatment with neuroserpin slows the progression of seizure activity throughout the CNS and results in significant neuronal survival in the hippocampus. Mutations in human neuroserpin result in a form of autosomal dominant inherited dementia which is characterized by the presence of intraneuronal inclusion bodies and is known as Familial Encephalopathy with Neuroserpin Inclusion Bodies.
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PMID:Neuroserpin: a selective inhibitor of tissue-type plasminogen activator in the central nervous system. 1498 20

Tissue plasminogen activator (tPA) is the predominant plasminogen activator present in the vascular and nervous systems. Prior studies of the two have emphasized different tPA sources; respectively, endothelium and neurons. A closer relationship is now suggested by evidence that the peripheral sympathetic nervous system synthesizes and infuses enzymatically active tPA into small artery walls and the microcirculation. TPA may thus be the only known neural product able to effect degradation of the artery wall extracellular matrix. This brief review considers historical and current indications for the existence of such an autonomically controlled system and some physiologic implications. Immunohistochemical tPA expression in small arteries and arterioles is more prominent in the outer wall sympathetic axon plexus than in endothelium. Its presence in nerve filaments beneath the seldom-studied adventitia was obscured in earlier localizations. The systemic impact of a neural distribution is suggested by a 60% reduction of blood tPA activity after chemical sympathectomy. TPA-bearing axons extend outward from ganglion neuron cell bodies to reach even thin-walled vasa vasora and uveal microvessels. Ganglion cell bodies synthesize and package tPA in vesicles for the long axoplasmic transport. Densely innervated intact vessels release much greater amounts of tPA in vitro than do larger vessels, indicating a high neuron tPA production capacity and a large storage reservoir available within axon networks. The influence of an autonomically controlled plasmin production within small artery walls on regulation of blood pressure and capillary perfusion awaits further investigation. Its possible role in the pathogenesis of vessel wall matrix degradations in aging, hypertension, and diabetes may also merit further consideration.
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PMID:Distribution of sympathetic tissue plasminogen activator (tPA) to a distant microvasculature. 1567 11

Since July 2002 we have been conducting a study of efficacy of prehospital thrombolytic therapy combined with subsequent endovascular procedures in the treatment of patients with acute myocardial infarction. Fifty nine patients received prehospital fibrinolysis with tissue-type plasminogen activator (TPA, n=28) or streptokinase (n=31) within 6 hours after onset of symptoms. TPA infusion compared with that of streptokinase was associated with smaller ischemic myocardial damage and lower frequency of side effects (3.6 and 38.7%, respectively). Angioplasty or stenting of infarct related arteries were carried out in 47 of these patients. The group of patients subjected to endovascular interventions was characterized by a low rate of in-hospital cardiac events and zero mortality.
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PMID:[Combination of prehospital systemic thrombolytic therapy with endovascular procedures in the treatment of patients with acute myocardial infarction]. 1582

The aim of the present study was to evaluate plasminogen activator activity (PAA), tissue-type plasminogen activator (t-PA) antigen level and plasminogen activator inhibitor-1 (PAI-1) antigen in normal canine gingival tissue samples, gingivitis as well as in different stages of periodontal disease. Gingival tissue from 141 adult dogs were analysed spectrophotometrically in order to determine PAA. The tissues were also examined histopathologically. The Sulcus Bleeding Index was used to evaluate the active and inactive phase of periodontal disease. T-PA antigen as well as PAI-1 antigen level was measured by ELISA. There was a significant increase of PAA and t-PA antigen in samples from inflamed gingival tissue compared with normal gingival tissue, while PAI-1 antigen was not detected in either normal or inflamed gingiva. As the severity of periodontal disease was increasing, PAA and t-PA antigen values were significantly higher in periodontitis tissue sample groups, according to the pattern: gingivitis<early periodontitis<moderate periodontitis<severe periodontitis (P<0.001). PAA and t-PA antigen were increased in samples from the inflamed gingival tissue with higher Bleeding Index, (heavy bleeding>moderate bleeding>slight bleeding, P<0.001). In conclusion, this study indicates that PAA and t-PA antigen level may be used to evaluate the evolution of periodontal disease in dog.
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PMID:A clinical study of plasminogen activator activity in gingival tissue in dogs with gingivitis and periodontitis. 1609 51

Ultrasound (US) has emerged as a new tool to treat ischemic stroke. The potential advantage of US is decreased risk of systemic bleeding complications due to its site-specific effect. Moreover, external application is noninvasive and is readily available. Experimental studies showed that low intensity (<or=2W/cm2) US safely enhanced thrombolytic drug activity within a wide range of frequencies (0.04-3.4 MHz). In humans, transcranial sonothrombolysis with mid-kHz frequencies showed an unacceptably high rate of intracranial bleeding, while the use of 2MHz yielded promising results in The Combined Lysis of Thrombus in Brain Ischemia Using Transcranial Ultrasound and Systemic TPA (CLOTBUST) study. This study was a phase II randomized clinical trial that included patients with middle cerebral artery (MCA) occlusion within 3 h of stroke onset, who were treated with standard dose of tissue plasminogen activator (t-PA). Residual flow in MCA was monitored with 2MHz US in one group, and the rate of complete recanalization and dramatic clinical recovery significantly increased as compared to t-PA alone. This chapter further discusses diagnosis of an acute occlusion and recanalization using the thrombolysis in brain ischemia (TIBI) waveform flow grading scale, application of fast track insonation protocol, and administration of US. Also, the potential enhancement of sonothrombolysis with microbubbles is discussed.
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PMID:Acute stroke: therapeutic transcranial Doppler sonography. 1729 Jan 34

Multiple sclerosis (MS) is an immune-mediated chronic inflammatory demyelinating disease of the central nervous system. It manifests as acute focal inflammatory demyelination and axonal loss with limited remyelination and results in the chronic multifocal sclerotic plaques. Previously published data showed impaired fibrinolysis in MS. Tissue plasminogen activator t-PA is a serine protease that catalyses the activation of plasmin, which mediates the effects of fibrinolytic system. Alu insertion/deletion (I/D) genetic polymorphism in TPA gene in MS patients has not been analysed previously. The major inhibitor of t-PA is plasminogen activator inhibitor-1 (PAI-1). Its gene expression is modulated by functional genetic polymorphism in the promoter (4G/5G). In the present study, an association of two genetic polymorphisms with MS, its progression and subtype were analysed. TPA DD/PAI-1 4G4G genotype combination has reached a borderline significance for reduced risk for MS (OR = 0.543, 95% CI 0.301-0.978, P = 0.04), suggesting a gene-gene interaction. The explanation for this interaction may be a complex interplay between these two pleiotropic proteins within the brain tissue and in plasma.
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PMID:PAI and TPA gene polymorphisms in multiple sclerosis. 1798 6

Tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) directly influence thrombus formation and degradation, and have been identified as risk factors for thromboembolic disease. Prior studies investigated determinants of t-PA and PAI-1 expression, but mainly in Caucasian subjects. The aim of this study was to identify the contributions of genetic and other factors to inter-individual variation in plasma levels of t-PA and PAI-1 in a large-scale population-based sample from urban West Africa. t-PA, PAI-1 and several demographic, anthropometric, and metabolic parameters were measured in 992 residents of Sunyani, the capital of the Brong-Ahafo region of Ghana. In addition, nine gene polymorphisms associated with components of the renin-angiotensin and fibrinolytic systems were determined. We found that BMI, systolic and diastolic blood pressure, total cholesterol, glucose, and triglycerides were all significant predictors of t-PA and PAI-1 in both females and males. In addition, a significant relationship was found between the PAI-1 4G/5G (rs1799768) polymorphism on PAI-1 levels in females, the TPA I/D (rs4646972) polymorphism on t-PA and PAI-1 in males, the renin (rs3730103) polymorphism on t-PA and PAI-1 in males, the ethanolamine kinase 2 (rs1917542) polymorphism on PAI-1 in males, and the renin (rs1464816) polymorphism on t-PA in females and on PAI-1 in males. This study of urban West Africans shows that t-PA and PAI-1 levels are determined by both genetic loci of the fibrinolytic and renin-angiotensin systems and other factors often associated with cardiovascular disease, and that genetic factors differ between males and females.
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PMID:Male-female differences in the genetic regulation of t-PA and PAI-1 levels in a Ghanaian population. 1895 68

Important biochemical constituents of the fibrinolytic system include tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1). In the current review, we aim to describe the genetic architecture of t-PA and PAI-1. Several genetic polymorphisms in the T-PA and PAI-1 gene have been found to be associated with t-PA and PAI-1 levels in different patient cohorts. However, these genetic variations explain only a minor part of the heritability of t-PA and PAI-1, suggesting that genes in other pathways may influence t-PA and PAI-1 levels, and that epistasis and gene-environment interactions may play an important role in determining plasma levels of t-PA and PAI-1. Several studies reported that interindividual variation in plasma levels of t-PA and PAI-1 are significantly influenced by common polymorphisms in genes from the renin-angiotensin and bradykinin systems. In addition, we and others documented several gene-environment interactions and epistatic effects of genetic polymorphisms in the renin-angiotensin, bradykinin, and fibrinolytic systems on plasma t-PA and PAI-1 levels. In future studies, we need to consider high-order interactions and additional polymorphisms in genes from other (unknown) pathways detected by genome-wide association studies to fully understand the complex genetic architecture of these important intermediate quantitative traits and thereby thrombosis.
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PMID:Genetic architecture of tissue-type plasminogen activator and plasminogen activator inhibitor-1. 1908 55

The present study was conducted to evaluate the antioxidant and anti-inflammatory activities of Jungia paniculata (DC.) A. Gray (Asteraceae), used traditionally in Peru. The dry leaves were extracted with methanol, 50% methanol, and water. The anti-inflammatory activity of this plant was studied using in vitro (nitric oxide production in RAW 264.7 macrophages and sPLA(2) inhibition assay) and in vivo (carrageenan-induced paw edema in rats and TPA-induced ear edema in mice) model systems. The antioxidant activity of extracts was studied using three in vitro model systems (DPPH(*) radical-scavenging assay, ABTS(*+) assay, and superoxide radical-scavenging activity). The results have been correlated with total phenolics and total flavonoids contents. In the NO test of the extracts of Jungia paniculata, no significant cytotoxicities were observed at the concentrations determined by MTT assay. Only the MeOH50 extract of Jungia paniculata significantly inhibited PLA(2) enzyme activity (82.3 +/- 2.6%). At 3 h, the 50% methanol extract of Jungia paniculata at an oral dose of 500 mg/kg showed significant suppression of carrageenan-induced rat paw edema (36.36%). The same extract induced a 93.99% reduction in TPA-induced edema in topical administration. The extracts exhibited a high antioxidant activity and contained high total levels of polyphenols and flavonoids. There was a significant linear correlation between total phenolics and flavonoids contents and antioxidant activity in the three models used. In conclusion, Jungia paniculata possesses anti-inflammatory and antioxidant properties, which confirm the use of this plant in folk medicine as a topical anti-inflammatory herbal.
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PMID:Anti-inflammatory and antioxidant activities of Jungia paniculata. 2067 77


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