Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.73 (urokinase-type plasminogen activator)
 10,685 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tetracyclines inhibit matrix metalloproteinases (MMPs) and reduce infarction volume following cerebral ischemia. In this thesis an involvement of urokinase could be proven. Cerebral ischemia in rats was induced for 3 h followed by 24 h reperfusion (suture model). Each 6 animals received orally either doxycycline or water. Doxycycline treatment began 10 days before ischemia. MMP-2 and MMP-9 were substantially decreased. The possibility of involvement of the endogenous MMP inhibitors in the MMP inhibiting mechanisms was excluded. The plasminogen activator uPA was significantly decreased by doxycycline indicating an MMP inhibiting mechanism including the plasminogen/plasmin system. In the doxycycline group, this resulted in a decreased damage to the cerebral microvessels and less loss of the basal lamina antigen collagen type IV. Hemoglobin extravasation was also significantly reduced. Our results suggest that doxycycline may have a potential use as an anti-ischemic compound since it provides microvascular protection by inhibiting the plasminogen system.
 ...
PMID:Doxycycline inhibits MMPs via modulation of plasminogen activators in focal cerebral ischemia. 1716 29

Heat shock proteins (HSPs) are reported to reduce inflammation and apoptosis in a variety of brain insults. Geranylgeranylacetone (GGA), developed as an antiulcer in Japan, has been known to induce HSP70 and to exert cytoprotective effects. In this study, we investigated whether GGA, as a specific HSP inducer, exerts therapeutic effects in experimentally induced intracerebral hemorrhage (ICH). ICH was induced with male Sprague-Dawley rats via the collagenase infusion. GGA (800 mg/kg) was administered via oral tube according to various schedules of treatment. The treatment with GGA, beginning before the induction of ICH and continuing until day 3, showed the reduction of brain water content and the increased level of HSP70 protein, as compared to the treatment with vehicle, although GGA started after the induction of ICH or administered as a single dose before ICH failed to up-regulate HSP70 and to reduce brain edema. The rats treated with GGA exhibited better functional recovery than those treated with vehicle. In the pre- and post- treatment group, inflammatory cells and cell death in the perihematomal regions were found to have been decreased. The treatment of GGA inhibited the mRNA expression of MMP-9, uPA, IL-6 and MIP-1, with concomitant increment of eNOS and phosphorylated STAT3 and Akt after ICH. We demonstrated that GGA induced a reduction in the brain edema along with marked inhibitory effects on inflammation and cell death after ICH.
 ...
PMID:Pharmacological induction of heat shock protein exerts neuroprotective effects in experimental intracerebral hemorrhage. 1720 4

Meningioma usually grows and expands into the brain, but invasion into the brain parenchyma is relatively rare. Meningioma arises from arachnoid cap cells, and infiltration into dura mater is the main growth pattern of meningiomas. However, little is known about the mechanism of meningioma invasion into the dura mater. In this study, seven specimens, including dural attachments, from seven cases of meningioma were used for immunohistochemical analysis. Matrix metalloproteinase (MMP)-1, -2, -9, urokinase-type plasminogen activator (uPA), vascular endothelial growth factors (VEGF), flt-1, E-cadherin, estrogen receptor (EgR), progesterone receptor (PgR), and aquaporin (AQP)-1, -4 were used as primary antibodies. There were several patterns of meningioma invasion into the dura mater: papillary-shaped invasion with destruction of dural structure, infiltration along the fibers of the dura mater, and invasion of several tumor cell units with fibroblast infiltration. Strong immunostaining was obtained with MMP-1, followed by AQP-1 and uPA, within the invading tumor cells. Neovasculature and extravasated erythrocytes, which stained with AQP-1, were also occasionally observed around the invading tumor cells. Simpson grade II removal of meningiomas results in high recurrence rates, and the inhibition of meningioma growth via dural invasion will facilitate improved remission in many cases with meningioma. In this study, MMP-1, AQP-1, and uPA are considered to have some role in the dural infiltration of meningioma cells. The fact that AQP-1 was highly expressed at the dural attachment and invading front of meningioma may indicate that dural invasion of the meningioma may be facilitated by AQP-1-induced water flow and neovascularization.
 ...
PMID:Dural invasion of meningioma: a histological and immunohistochemical study. 1809 14

The Bowman-Birk inhibitor (BBI) is a small water-soluble protein present in soybean and almost all monocotyledonous and dicotyledonous seeds. The molecular size of BBI ranges from 1,513 Da to about 20,000 Da. BBI is to seeds what alpha(1)-antitrypsin is to humans. Soy-based food products rich in BBI include soybean grits, soymilk, oilcake, soybean isolate, and soybean protein concentrate. BBI is stable within the pH range encountered in most foods, can withstand boiling water temperature for 10 min, resistant to the pH range and proteolytic enzymes of the gastrointestinal tract, bioavailable, and not allergenic. BBI reduces the proteolytic activities of trypsin, chymotrypsin, elastase, cathepsin G, and chymase, serine protease-dependent matrix metalloproteinases, urokinase protein activator, mitogen activated protein kinase, and PI3 kinase, and upregulates connexin 43 (Cx43) expression. Several studies have demonstrated the efficacy of BBI against tumor cells in vitro, animal models, and human phase IIa clinical trials. FDA considers BBI as a drug. In 1999, FDA allowed a health claim on food labels stating that a daily diet containing 25 grams of soy protein, also low in saturated fat and cholesterol, may reduce the risk of heart disease [corrected] This review highlights the biochemical and functional food properties of the Bowman-Birk inhibitor.
 ...
PMID:The biochemical and functional food properties of the bowman-birk inhibitor. 1827 67

Seasonal variation in stratum corneum (SC) biophysical and biological characteristics has been described previously. In particular, the winter season has been shown to affect more severely the properties of facial skin compared with forearm skin. Moreover, when compromised, such as in dry skin conditions, facial SC has been shown to contain increased inflammatory cytokines and proteases. Nevertheless, there have been no comparative studies of the activities and depth activity of several proteases in the SC on different body sites and at different times of the year. In this study, we examined the distribution of key serine protease activities (kallikrein 5, kallikrein 7, urokinase, plasmin and a tryptase-like enzyme) in different layers of the SC on the cheek and the forearm by analysis of consecutive tape strippings of healthy Caucasian subjects during winter and summer. The protein content of the tape strippings was quantified by absorption measurements with a recently developed and novel infrared densitometer SquameScan 850A while the SC enzyme activities were determined using fluorogenic peptide substrates. Transepidermal water loss (TEWL), skin pH and skin hydration were higher on the cheek than on the forearm. In the same way, the activity of the inflammatory-related proteases plasmin, urokinase and tryptase was approximately five to eight times and the activity of the desquamatory-related proteases kallikrein 5 and kallikrein 7 approximately two to four times higher on the cheek than on the forearm. There were no gender-related differences in these enzyme activities except for the increased kallikrein 7 in the forearm skin of the female subjects in winter. Reduced kallikrein 5 was associated with increased SC cohesion, as judged by increased protein removal, in forearm skin in the winter months of the year although the skin was clinically normal. It can be concluded that (i) protected skin areas show lower TEWL, skin pH and skin hydration and less protease activities than skin areas that are exposed to the environment, possibly indicating subclinical inflammation on these body sites, (ii) in normal healthy forearm skin, the outer SC exhibits greater serine protease activity than its deeper layers, (iii) compared with the forearm, urokinase- and plasmin-like activities are elevated on SC strippings from the cheek, confirming activation of the plasminogen cascade, and (iv) tryptase-like activity in the SC is also elevated in samples from the cheek, possibly indicating involvement of mast cells in these barrier-compromised body sites or the synthesis of a novel tryptase-like enzyme by keratinocytes. Although elevation of the activities of urokinase, plasmin, kallikrein 5, kallikrein 7 and now a tryptase-like enzyme was observed on SC derived from skin of clinically normal cheeks, we anticipate even higher activities in skin conditions where the epidermal barrier is further impaired.
 ...
PMID:Profiling of serine protease activities in human stratum corneum and detection of a stratum corneum tryptase-like enzyme. 1848 49

A water-soluble, ligand-bound polymer has been synthesized for the purpose of isolation of urokinase, an important plasminogen activator. The affinity polymer was formed by copolymerizing N-acryloyl-m-aminobenza-midicine and acrylamide in the absence of oxygen. An affinity ultrafiltration process was then developed for isolating urokinase from an artificial solution containing peroxidase and urokinase and from a crude urine source. The process yields were determined to be 86% and 49%, respectively. The recovered urokinase exhibited a specific activity close to that of the highest commercial grade. This article also presents a new technique for assaying urokinase by coupling plasminogen with L-benzoyl arginine-p-nitroanilide (L-BAPNA), an inexpensive chromogenic substrate.
 ...
PMID:Isolation of urokinase by affinity ultrafiltration. 1858 35

Stabilization of proteins through proper formulation is an important challenge for the pharmaceutical industry. Two approaches for stabilization of proteins in solution are discussed. First, work describing the effect of additives on the thermally induced denaturation and aggregation of low molecular weight urokinase is presented. The effects of these additives can be explained by preferential exclusion of the solute from the protein, leading to increased thermal stability with respect to denaturation. Diminished denaturation leads to reduced levels of aggregation. The second approach involves stoichiometric replacement of polar counter ions (e.g., chloride, acetate, etc.) with anionic detergents, in a process termed hydrophobic ion pairing (HIP). The HIP complexes of proteins have increased solubility in organic solvents. In these organic solvents, where the water content is limited, the thermal denautration temperatures greatly exceed those observed in aqueous solution. In addition, it is possible to use HIP to selectively precipitate basic proteins from formulations that contain large amounts of stabilizers, such as human serum albumin (HSA), with a selectivity greater than 2000-fold. This has been demonstrated for various mixtures of HSA and interleukin-4. (c) 1995 John Wiley & Sons, Inc.
 ...
PMID:Approaches for increasing the solution stability of proteins. 1862 15

Emerging data suggests the serine proteases, tissue plasminogen activator (tPA), and urokinase plasminogen activator (uPA), may play a detrimental role in traumatic states leading to compromise of the blood brain barrier (BBB). The purpose of our study was to define the role of endogenous tPA and uPA on the BBB following peripheral burn injuries. Adult male Sprague-Dawley rats (n=46) were studied in control and thermal injury groups. Rats were anesthetized and submerged in 100 degrees C water for 6s producing a third degree burn affecting 60-70% of the total body surface area. BBB dysfunction was then evaluated by measuring the amount of Evans blue and by calculating the water content in the brain. Levels of tPA and uPA mRNA in the brain were determined with real-time polymerase chain reaction (PCR) at 3 and 7h post-injury. Results showed an increase in the brain water content and the presence of Evans blue in the brain tissue of thermally injured rats, temporally associated with an increased expression of endogenous tPA and uPA. Our study demonstrates that peripheral thermal injury does induce an increase in the permeability of the BBB. A possible mechanism may be an increased expression of tPA and uPA.
 ...
PMID:Blood brain barrier (BBB) dysfunction associated with increased expression of tissue and urokinase plasminogen activators following peripheral thermal injury. 1871 5

Accidental intra-arterial injection of drugs is a sporadic complication in i.v. drug addicts. A 22-year-old drug-abuser injected flunitrazepam tablets dissolved in tap water into her left femoral artery and presented with clinical signs of acute ischaemia of the left leg. Severe rhabdomyolysis developed within 5 hours after the injection. Selective arterial catheter angiography showed an acute occlusion of the posterior tibial artery. Combination therapy with i.a. urokinase, i.a. prostaglandines and i.v. anticoagulation resulted in re-opening of the obstructed distal artery and complete cessation of symptoms.
 ...
PMID:Acute ischaemia of the leg following accidental intra-arterial injection of dissolved flunitrazepam tablets. 1900 50

There are indications of elevation of some inflammatory serine proteases in barrier damaged skin (e.g. plasmin and urokinase). Moreover, many other serine protease activities are present such as desquamatory enzymes as well as a newly detected tryptase-like serine protease. However, the activities of these proteases have never been correlated with stratum corneum (SC) barrier function. The activity of extractable key serine proteases (SC trypsin-like kallikreins, SC chymotrypsin-like kallikreins, SC tryptase-like serine protease, urokinase and plasmin) was measured from the outermost layers of SC obtained from facial tape strippings in clinically normal subjects. The protein content of the tape strippings was quantified by absorption measurements with the novel infrared densitometer SquameScan 850A and the protease activities by the use of fluorogenic peptide substrates. SC barrier function, SC hydration and skin surface pH were measured using AquaFlux, NOVA dermal phase meter and Skin-pH-Meter, respectively. As expected, SC hydration was reduced with increased transepidermal water loss (TEWL) values indicative of barrier impairment. Surprisingly, SC chymotrypsin-like activity showed no correlation with hydration or TEWL, whereas all other enzymes positively correlated with impaired barrier function and some were statistically significant: SC trypsin-like kallikreins (R(2 )=0.66, P < 0.01), SC tryptase-like enzyme (R(2 )=0.95, P < 0.001), plasmin (R(2 )=0.86, P < 0.001) and urokinase (R(2 )=0.50, P < 0.05). All enzymes except urokinase also negatively correlated with SC hydration. Elevated levels of SC serine proteases have been associated with some dermatological disorders, such as atopic dermatitis, psoriasis and rosacea but these results indicate that these enzymes are also elevated with milder forms of barrier disruption, which is not clinically evident as irritated skin. As these proteases are elevated in the SC, they will also be elevated in the epidermis where they can be involved in neurogenic inflammation and epidermal barrier impairment via activation of the protease-activated receptors. These results highlight the need for using serine protease inhibitors especially for urokinase and plasmin, SC tryptase-like serine protease and possibly SC trypsin-like kallikreins even in milder forms of barrier damage.
 ...
PMID:Increased basal transepidermal water loss leads to elevation of some but not all stratum corneum serine proteases. 1909 44


<< Previous 1 2 3 4 5 6 7 8 Next >>