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)

Messenger RNA of the phorbol ester-induced 48kDa protein from human melanoma cells (Bowes) was isolated, characterized and used to study the protein processing. The 48kDa mRNA is induced simultaneously with that of tissue-type plasminogen activator. This induction is prominent as shown by sedimentation profiles on linear sucrose gradients. The mRNA can be isolated by classical phenol extractions, has a poly(A)-tail and sediments with a coefficient of 20 S. Translation in reticulocyte lysates yields a 48kDa protein whether the translation is modified with canine pancreas microsomal membranes or not. Analysis of 48kDa mRNA translation products by sodium dodecyl sulphate/polyacrylamide gel electrophoresis showed that the phorbol ester-induced 48kDa is a monomeric one-chain polypeptide. Glycosylation could not be detected, nor signal peptide cleaving, suggesting that it is a non-secreted intracellular protein.
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PMID:Messenger RNA for a phorbol-ester induced 48,000 dalton protein from human melanoma cells. 308 63

The effects of synthetic and natural phenol polymers on the release of plasminogen activator were examined on an isolated vascular preparation of the pig ear. Of the synthetic phenol polymers, the products of caffeine acid and 3,4-dihydroxyphenylacetic acid were found to raise the activity of plasminogen activator. As far as the natural polymers of phenol are concerned, only sodium humate was found to produce an action similar to that of the products of caffeinic acid and 3,4-dihydroxyphenylacetic acid.
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PMID:[Effect of phenol ring polymers on the release of plasminogen activators]. 653 11

A human melanoma cell line (Bowes), which secretes extrinsic (tissue-type) plasminogen activator, was used as a source for the preparation of mRNA for extrinsic plasminogen activator. The cells were lysed and total RNA was extracted with the phenol method. A poly(A)-rich RNA fraction was isolated by affinity chromatography on oligo(dT)-cellulose. This preparation was translated by oocytes into (a) protein(s) that had biological activity in the assay for extrinsic plasminogen activator. On sucrose gradient centrifugation the translatable fraction of the RNA migrated with a sedimentation coefficient of approximately 19 S, a value compatible with the molecular weight of extrinsic plasminogen activator (70 000). The translation product was characterized as being similar to or identical with authentic extrinsic plasminogen activator by the following criteria: (a) serological cross-reactivity with purified extrinsic plasminogen activator in neutralization and immunoprecipitation reactions; (b) plasminogen dependency of fibrinolytic activity and (c) apparent molecular weight of 70 000 on sodium dodecyl sulphate/polyacrylamide gel electrophoresis.
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PMID:Messenger RNA for human tissue plasminogen activator. 719 59

Staplabin (0.3-0.6 mM), a fungal triprenyl phenol, enhanced 3-fold the plasminogen activator-catalyzed activation of Glu-plasminogen and Lys-plasminogen as well as their binding to fibrin. Staplabin was not stimulatory to the amidolytic activity of plasmin and plasminogen activators. Even in the presence of epsilon-aminocaproic acid (EACA) and fibrinogen fragments, allosteric effectors for Glu-plasminogen, staplabin increased the activation of both forms of plasminogen. In size-exclusion chromatography of Glu-plasminogen and Lys-plasminogen, the molecular elution time, which varies as the conformation of a protein changes, was shortened by staplabin. These results suggest that staplabin causes plasminogens to be more susceptible to activation and fibrin binding by inducing a conformational change that is, at least in part, different from that induced by EACA and fibrinogen fragments.
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PMID:Enhancement of fibrin binding and activation of plasminogen by staplabin through induction of a conformational change in plasminogen. 941 95

Both tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 2 (PAI-2) are important proteolysis factors present in inflamed human periodontal tissues. The aim of the present study was to investigate the effect of lipopolysaccharide (LPS) on the synthesis of t-PA and PAI-2 by human gingival fibroblasts (HGF). LPS from different periodontal pathogens including Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis and Fusobacterium nucleatum were extracted by the hot phenol water method. The levels of t-PA and PAI-2 secreted into the cell culture media were measured by enzyme-linked immunosorbent assays (ELISA). The mRNA for t-PA and PAI-2 were measured by RT-PCR. The results showed t-PA synthesis was increased in response to all types of LPS studied and PAI-2 level was increased by LPS from A. actinomycetemcomitans and F. nucleatum, but not P. gingivalis. When comparing the effects of LPS from non-periodontal bacteria (Escherichia coli and Salmonella enteritidis) with the LPS from periodontal pathogens, we found that the ratio of t-PA to PAI-2 was greater following exposure of the cells to LPS from periodontal pathogens. The highest ratio of t-PA to PAI-2 was found in those cells exposed to LPS from P. gingivalis. These results indicate that LPS derived from periodontal pathogens may cause unbalanced regulation of plasminogen activator and plasminogen activator inhibitor by HGF and such an effect may, in part, contribute to the destruction of periodontal connective tissue through dysregulated pericellular proteolysis.
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PMID:Effect of lipopolysaccharide from periodontal pathogens on the production of tissue plasminogen activator and plasminogen activator inhibitor 2 by human gingival fibroblasts. 1124 1

Future surgical strategies to restore neurological function in peripheral nerve loss may involve replacement of nerve tissue with cultured Schwann cells using biodegradable guiding implants. Random copolymers of trimethylene carbonate and epsilon caprolactone (P(epsilonCL-TMC), 50: 50) have been synthesized by ring opening polymerization using rare earth alkoxides as initiator. Their potential use as nerve guide repairs has been assessed through indirect and direct in vitro biocompatibility tests and in vivo soft tissue response to EDI subclass macrophages. In vitro, we exposed monolayers of human skin fibroblasts and an established continuous cell line (Hela) to liquid extracts (either pure or diluted in the culture medium) of epsilonCL-TMC copolymer including positive (phenol) and negative controls. Then, colorimetric assays (Neutral red and MTT) were performed. The extracts of epsilonCL-TMC induced no significant cytotoxic effect. We also exposed in vitro Schwann cells to pieces of P(epsilonCL-TMC) and P(LA-GA) copolymers. We evaluated cell attachment at 1 and 3 h by measuring the activity of the lysosomal enzyme (N-acetyl-beta-hexosaminidase) and cell proliferation at 1, 3, 6 and 9 days by measuring the cell metabolic activity (MTT assay). Values for attachment slightly decreased between 1 and 3 h but were significantly higher than on agars (negative control). Cells plated on epsilonCL-TMC showed a rate of proliferation comparable with that of normalized controls and higher than on PGA-PLA at day 9. Finally, we evaluated in vivo the soft tissue response after implantation of cylindrical tubes of P(epsilonCL-TMC) and P(LA-GA) copolymers with an immunohistochemistry staining procedure for the newly recruited ED1 macrophages. An image analysis system automatically measured the optical density of labelled positive ED1 cells at 9, 21 and 60 days after implantation. epsilonCL-TMC copolymer showed a mild soft tissue reaction with no adverse chronic inflammatory reaction. These data allowed us to consider this conduit as a potential effective substitute in nerve repair. El sevier Science Ltd. All rights reserved.
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PMID:Study of a (trimethylenecarbonate-co-epsilon-caprolactone) polymer--part 2: in vitro cytocompatibility analysis and in vivo ED1 cell response of a new nerve guide. 1157 69

An extensive structural manifold of short hydrogen bond-mediated, active site-directed, serine protease inhibition motifs is revealed in a set of over 300 crystal structures involving a large suite of small molecule inhibitors (2-(2-phenol)-indoles and 2-(2-phenol)-benzimidazoles) determined over a wide range of pH (3.5-11.4). The active site hydrogen-bonding mode was found to vary markedly with pH, with the steric and electronic properties of the inhibitor, and with the type of protease (trypsin, thrombin or urokinase type plasminogen activator (uPA)). The pH dependence of the active site hydrogen-bonding motif is often intricate, constituting a distinct fingerprint of each complex. Isosteric replacements or minor substitutions within the inhibitor that modulate the pK(a) of the phenol hydroxyl involved in short hydrogen bonding, or that affect steric interactions distal to the active site, can significantly shift the pH-dependent structural profile characteristic of the parent scaffold, or produce active site-binding motifs unique to the bound analog. Ionization equilibria at the active site associated with inhibitor binding are probed in a series of the protease-inhibitor complexes through analysis of the pH dependence of the structure and environment of the active site-binding groups involved in short hydrogen bond arrays. Structures determined at high pH (>11), suggest that the pK(a) of His57 is dramatically elevated, to a value as high as approximately 11 in certain complexes. K(i) values involving uPA and trypsin determined as a function of pH for a set of inhibitors show pronounced parabolic pH dependence, the pH for optimal inhibition governed by the pK(a) of the inhibitor phenol involved in short hydrogen bonds. Comparison of structures of trypsin, thrombin and uPA, each bound by the same inhibitor, highlights important structural variations in the S1 and active sites accessible for engineering notable selectivity into remarkably small molecules with low nanomolar K(i) values.
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PMID:Elaborate manifold of short hydrogen bond arrays mediating binding of active site-directed serine protease inhibitors. 1274 21

A possible mechanism for phenol-induced pemphigus lesions in genetically predisposed individuals is proposed that accounts for in vitro observations and cases of biochemical acantholysis, as well as the in vivo acantholysis in pemphigus induced by phenols. The mechanism involves the induction of interleukin-1a and tumor necrosis factor-a release by keratinocytes. These cytokines in turn have been shown to be involved in the regulation and synthesis of complement and proteases like plasminogen activator, which have been implicated in the pathogenesis of acantholysis in pemphigus vulgaris.
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PMID:A possible mechanism for phenol-induced pemphigus. 1652 79

This paper describes the structure-activity relationship in a series of tripeptidyl diphenyl phosphonate irreversible urokinase plasminogen activator (uPA) inhibitors, originally derived from an arginyltripeptide. uPA is considered an interesting target in anticancer drug design. The selectivity of these inhibitors for uPA is enhanced by the optimization of the P4 position. The most interesting compound shows an IC(50) of 5 nM, with a selectivity index of more than 3000 toward other Arg/Lys-specific proteases such as tissue-type plasminogen activator, plasmin, factor Xa, and thrombin. A synthetic strategy for the preparation of small libraries of diphenyl phosphonate analogues of capped tripeptides is described. It is shown that uPA is irreversibly inhibited, and interactions with the active site were modeled. Finally, a diparacetamol phosphonate analogue was developed to circumvent the release of cytotoxic phenol.
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PMID:Diphenyl phosphonate inhibitors for the urokinase-type plasminogen activator: optimization of the P4 position. 1697 Apr 3

Pemphigus is an autoimmune disease that results from the interaction between predisposing genetic factors and exogenous factors, the most common environmental factors being drugs and food. Topical phenol has induced pemphigus in one patient. Drugs and foods that induce pemphigus are divided into three main groups according to their chemical structure: thiols (containing a sulfhydryl group), phenol, nonthiol nonphenol. Thiol and phenol compounds can induce acantholysis in tissue cultures in vitro. The suggested mechanisms for thiol acantholysis include direct biochemical impairment of cell adhesion, protease activation and immunological reaction with the formation of a neoantigen. Possible mechanisms of phenol-induced pemphigus include the induction of IL-1alpha and TNF-alpha release by keratinocytes. These cytokines have been shown to be relevant in the regulation and synthesis of complement and proteases, like plasminogen activator, which has been implicated in the pathogenesis of acantholysis in pemphigus vulgaris. Avoiding exposure of genetically predisposed individuals to these factors is important in treating and preventing this disease.
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PMID:Pemphigus can be induced by topical phenol as well as by foods and drugs that contain phenols or thiols. 1716 23


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