Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.7 (plasmin)
 9,023 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypophysectomized rats were treated for 6 days with 200 mug per day of either human chorionic somatomammotropin, human pituitary growth hormone, plasmin-modified human pituitary growth hormone, or ovine prolactin. All hormone preparations except ovine prolactin enhanced the ability of the pancreases of hypophysectomized rats to secrete insulin in the isolated pancreas perfusion system.
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PMID:Enhancement of insulin secretion by human chorionic somatomammotropin and related hormones. 13 69

The action of fibrinolysin (plasmin; EC 3.4.21.7) on ovine prolactin has been investigated. It was found that the enzyme selectively cleaves the bond between Met-53 and Ala-54. The two fragments, PRL-(1-53) and PRL-(54-199), have been purified and characterized. A recombinant molecule has been obtained by noncovalent interaction of PRL-(1-53) and PRL-(54-199). The recombined protein behaves nearly identically to the parent hormone in circular dichroism spectra and exclusion chromatography. The recombinant possesses full immunoreactivity, as revealed by gel double-diffusion and complement fixation. However, the recombined protein exhibits low prolactin activity in the pigeon crop-sac test.
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PMID:Two fragments from fibrinolysin digests of ovine prolactin: characterization and recombination to generate full immunoreactivity. 14 84

The present study was undertaken to assess the effects of prolactin (PRL) on gonadotropin-induced plasmin generation in the in vitro-perfused rabbit ovary. The ovarian plasmin activity was determined by measuring plasmin bound to its major inhibitor, alpha 2-plasmin inhibitor (alpha 2 PI-Plm). In the first experiment, exposure to hCG enhanced ovarian alpha 2 PI-Plm generation from 1.2 +/- 0.3 ng/min/ovary in unstimulated ovaries to 2.9 +/- 0.3 ng within 2 h. The concentration of alpha 2 PI-Plm reached a maximum at 4 h and then declined. A second peak occurred 8 h after hCG administration; however, the ovarian alpha 2 PI-Plm generation without hCG was very low throughout the entire perfusion period. In the subsequent experiment, the addition of PRL(10-10(3) ng/ml) to the perfusate inhibited hCG-induced ovulation in a dose-dependent manner. Exposure to PRL at 10(3) ng/ml significantly (p less than 0.05) inhibited hCG-induced alpha 2 PI-Plm generation in ovaries throughout the entire perfusion period. Furthermore, PRL inhibited hCG-stimulated alpha 2 PI-Plm generation at 4 h after hCG administration in the perfused rabbit ovaries in a dose-dependent manner. In conclusion, PRL directly inhibits hCG-induced ovulation in rabbit ovary, at least in part, by a mechanism depending upon inhibition of the plasmin-generating system in the preovulatory follicles.
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PMID:Effects of prolactin on ovarian plasmin generation in the process of ovulation. 153 14

We have established 13 hybridoma cell lines which secrete mouse IgG1 monoclonal antibodies (McAbs) to human growth hormone (hGH). Binding affinity and binding specificity of McAbs were analyzed by competitive radioimmunoassay. Among these McAbs, CL. B1 showed a high affinity of 9.8 x 10(8) l/mol, and all McAbs so far tested showed very weak cross-reactivity or none at all with human prolactin (hPRL) and human chorionic somatomammotropin (hCS; human placental lactogen). Analysis of binding sites of McAbs using hGH variant and fragments in both ELISA and RIA demonstrated that McAbs could be classified into two groups. All the McAbs obtained in this study bound to plasmin-digested fragment S2 (hGH 1-134 and 141-191) and fragment alpha 3 (hGH 1-134 and 147-191). However, five (such as 1D2) out of 13 McAbs bound to fragment F1 (hGH 1-134) and others (such as CL. B1) did not. The McAb CL. B1 in the latter group showed low affinity with 20 K hGH (residue 32-46 deleted in native 22 K hGH) in contrast to high affinity with hGH (22 K). This suggests that the former McAbs recognize an epitope located at the N-terminal two-third part of hGH. In contrast, the McAbs of the latter group are likely to recognize three-dimensional structure of native 22 K hGH.
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PMID:Monoclonal antibodies which preferentially bind to 22 K human growth hormone rather than its 20 K variant. 247 33

It has been previously demonstrated that commercial bacterial fibrinolysin (EC 3.4.21.7) selectively cleaves the bond between Met-53 and Ala-54 in ovine prolactin (199 amino acids). A one-step purification procedure on DEAE-cellulose for Protease F, which is the active component of bacterial fibrinolysin, and properties of the purified enzyme are reported. The enzyme is homogeneous as judged by acrylamide gel electrophoresis. Its molecular weight, calculated from gel filtration experiments on Sephadex G-100, is around 13,800. Amino acid analyses do not reveal the presence of any half-cystines. The presence of one tryptophan residue per enzyme molecule was resolved from the fluorescence spectrum. Amino terminal analysis showed that leucine was at the amino terminal position. Protease F hydrolyzes casein and synthetic specific substrates for chymotrypsin and elastase esterases but not for trypsin esterases. It is fully inhibited by phenylmethylsulfonyl fluoride, by chicken ovoinhibitor, and by Chymotrypsin Inhibitor I from potatoes but not by the trypsin-chymotrypsin inhibitors from soybeans and chick peas or by tosyl-L-phenylalanine chloromethyl ketone. The enzyme is stable at room temperature and in the cold, it is not affected by dialysis or by freezing and thawing, but it is inactivated during freeze-drying. The circular dichroism spectra of Protease F indicate an approximate 20% alpha-helix content of the enzyme with a considerable similarity to those of subtilisin, elastase, and beta-trypsin. The relatively low molecular weight of Protease F, the absence of intrachain disulfide bridges, and the fact that it is inhibited by several, but not all, chymotrypsin inhibitors suggest that it may differ phylogenetically from the known serine proteases.
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PMID:Purification and properties of protease F, a bacterial enzyme with chymotrypsin and elastase specificities. 622 44

The recombined molecule obtained by complementation of two fibrinolysin fragments of ovine prolactin (oPRL) has been characterized by radioimmunoassay and radioreceptor assay. The recombinant alone exhibits very low radioimmunoreactivity and radioreceptor activity. However, in the presence of excess fragment oPRL-(1-53), which does not compete with oPRL in either assay, the recombinant has 101% of the radioimmunoreactivity and only 13% of the radioreceptor activity. The result shows that the low activity of the recombinant when assayed alone is due to dissociation of the molecule. When the molecule is completely in the recombined form in the presence of excess oPRL-(1-53), it retains full immunoreactivity but only part of the radioreceptor activity.
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PMID:Radioimmunoreactivity and receptor-binding activity of the recombined molecule obtained by complementation of two fibrinolysin fragments of ovine prolactin. 626 55

The equilibrium characteristics of the recombined molecule formed by noncovalent interaction of two fibrinolysin fragments of ovine prolactin (oPRL) have been studied with fluorescence polarization. Fluorescein isothiocyanate (isomer I) was used to label oPRL-(1-53), creating a fluorescent peptide indistinguishable from the unlabeled fragment in the complementation reaction with oPRL-(54-199). The dissociation constant of the recombinant prolactin was 0.144 microM at 30 degrees C, with a free energy of dissociation of 9.50 kcal/mol.
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PMID:Ovine prolactin: equilibrium characteristics of the recombinant molecule formed by noncovalent interaction of two fibrinolysin fragments by fluorescence polarization. 645 91

The present study was undertaken to investigate the effects of prolactin (PRL) on gonadotropin-induced ovulation and the biosynthesis of prostaglandin (PG), leukotriene (LT), and plasmin in in vitro perfused rabbit ovaries. The addition of PRL to the perfusate inhibited hCG-induced ovulation in vitro in a dose-dependent manner. Although exposure to hCG significantly increased PGF2 alpha, PGE2, and LTB4 production by perfused rabbit ovaries, PRL did not affect the secretion rates of PGs and LTB4 stimulated by hCG administration. The ovarian plasmin generation was determined by measuring the amount of plasmin bound to its major inhibitor, alpha 2-plasmin inhibitor (alpha 2PI-Plm). Exposure to hCG enhanced biphasically the ovarian secretion rate of alpha 2 PI-Plm, while PRL at a dose of 10(3) ng/ml significantly inhibited the hCG-stimulated generation of alpha 2 PI-Plm in ovaries throughout the entire perfusion period. A significant correlation was observed between ovulatory efficiency and ovarian plasmin generation in the PRL-treated ovaries. Additionally, PRL inhibited intrafollicular concentrations of alpha 2 PI-Plm in hCG-treated ovaries in a dose-dependent manner. These observations substantiate an essential role for a plasma-generating system in the cascade of events leading to ovulation. In conclusion, PRL may act directly on the ovary and block ovulation, at least in part, via the inhibition of ovarian plasmin generation.
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PMID:Prolactin inhibits ovulation by reducing ovarian plasmin generation. 808 Sep 10

Urokinase plasminogen activator (uPA) is involved in proteolysis of extracellular matrix during development and tumor cell invasion. In the present study, we examined the regulation of uPA in hormone-responsive, noninvasive mammary epithelial cells by using fibrinolytic and caseinolytic enzyme activity assays. Urokinase PA expression was activated after contact with fibrin and initiation of cell-cell interactions that were mediated by E-cadherin. Fibrinolysis occurred in zones surrounding cellular aggregates. Stromal matrix proteins that disrupted aggregation or anti-E-cadherin antibodies that inhibited cellular compaction inhibited fibrinolysis perhaps by increasing cell-matrix adhesion or preventing E-cadherin signaling, respectively. Aggregation required the presence of divalent cations and was inhibited by serum and ethylene diaminetetraacetic acid, whereas serine protease inhibitors reduced uPA activity without affecting aggregation. Inhibitors of PA (type 2; PAI-2) and a specific antisense uPA oligonucleotide also reduced enzymatic activity, suggesting that fibrinolysis depends on translational regulation of uPA. In addition, the activation of plasmin from plasminogen was inhibited by anti-E-cadherin antibodies and PAI-2, consistent with a role for uPA. The data also support a role for transcriptional regulation of uPA activity because treatment of cells with progesterone, hydrocortisone, or dexamethasone inhibited uPA activation on fibrin without affecting cellular aggregation. Estradiol and insulin did not alter, whereas human chorionic gonadotropin and prolactin increased uPA activity. The expression of the 55-kDa uPA activity was consistent with specific hormone action and correlated with protein expression by immunoblotting. Therefore, the alteration of downstream signaling events by hormones may affect uPA production. These results indicate that uPA is an enzyme that may be important in the degradation of extracellular matrix during development and that specific E-cadherin interactions and hormones can regulate its activity. Investigation of the regulation of uPA in these cells may be useful in understanding and manipulating mammary gland remodeling. J. Cell. Physiol. 181:1-13, 1999. Published 1999 Wiley-Liss, Inc.
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PMID:Regulation of urokinase plasminogen activator (uPA) activity by E-cadherin and hormones in mammary epithelial cells. 1045 48

This study aims to investigate the mechanism by which prolactin and GH interact to maintain mammary epithelial cell function in the rat. IGF-I is an important survival factor for the mammary gland and we have demonstrated that the effects of GH and prolactin involve IGF-I. GH acts by increasing IGF-I whilst prolactin acts by inhibiting the expression of IGFBP-5 from the mammary epithelium. During mammary involution, when serum prolactin levels decline, IGFBP-5 expression is dramatically upregulated and it binds with high affinity to IGF-I preventing IGF-I interaction with the IGF-receptor and thus leading to epithelial cell apoptosis. We have identified a specific interaction of IGFBP-5 with alpha s2-casein. This milk protein has also been shown to bind plasminogen and its activator tissue-type plasminogen activator (tPA) leading to enhanced conversion of plasminogen to plasmin. Plasmin is an important initiator of re-modelling of the extracellular matrix during mammary involution. A potential interaction between the cell death and extracellular matrix remodelling is evident from the observation that IGFBP-5 binds to plasminogen activator inhibitor-I (PAI-1). We thus hypothesized that IGFBP-5 could activate cell death by sequestration of IGF-I and activate plasminogen cleavage by sequestering PAI-1. In support of this hypothesis we have shown that both prolactin and GH inhibit tPA activity and plasminogen activation in the involuting mammary gland. Our results suggest that GH and prolactin inhibit cell death and ECM remodelling via the IGF-axis and also indicate a novel role for the milk protein alpha s2-casein in this process. We have now established lines of transgenic mice expressing IGFBP-5 on the beta-lactoglobulin promoter to explore its function in greater detail.
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PMID:Insulin-like growth factor binding protein-5 (IGFBP-5) potentially regulates programmed cell death and plasminogen activation in the mammary gland. 1095 8


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