Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cardio-protective mechanisms of EGb 761, an extract of Ginkgo biloba leaves, on myocardial ischemia-reperfusion injury were investigated using rabbits subjected to 30 minutes of regional cardiac ischemia and 120 min of reperfusion under anesthesia. Compared to the saline perfused group, EGb 761 treatment (10 mg/kg, injected into the coronary artery) significantly inhibited the increase in lipid peroxidation and maintained total and CuZn-SOD levels in both plasma and tissue during and at the end of reperfusion. Both the decrease in tissue type plasminogen activator (t-PA) and the increase in plasminogen activator inhibitor-1 (PAI-1) caused by ischemia-reperfusion were also significantly suppressed by EGb 761 treatment. Furthermore, the ultrastructure of the myocytes of the EGb 761 treated heart was slightly damaged after ischemia-reperfusion, while the control ischemic-reperfused hearts demonstrated severe histological damages such as swelling and vacuolization of the mitochondria. These results suggest that EGb 761 protects hearts by its antioxidant properties and by its ability to adjust fibrinolytic activity.
Biochem Mol Biol Int 1995 Jan
PMID:Efficiency of Ginkgo biloba extract (EGb 761) in antioxidant protection against myocardial ischemia and reperfusion injury. 773 27

Effects of phorbol myristate acetate (PMA), dibutyryl cyclic AMP (dbcAMP), 6-dimethylaminopurine (6-DMAP), and okadaic acid (OA) on plasminogen activator (PA) activity in porcine oocyte-cumulus cell complexes (POCC) in vitro were determined. Cumulus cell-enclosed oocytes were collected from 1-4 mm antral follicles and cultured in TCM-199 with 0.3% polyvinylpyrrolidone for 48 hr. PA activities in POCC were quantified using SDS-PAGE, casein-agar zymography, and densitometry. Two plasminogen-dependent lytic zones (93-96 kD and 71-79 kD) were observed in POCC. Addition of amiloride to the zymography, a competitive inhibitor of urokinase-type PA, failed to reduce activities in either zone, suggesting that the 71-79 kD band is a tissue-type PA (tPA) and the 93-96 kD band is possibly a tPA-inhibitor complex. Changes in PA activity due to the various treatments were expressed relative to the PA activity in 40 POCC. Increasing dbcAMP increased PA (P < 0.05) activity in dose-dependent fashion, whereas 6-DMAP and 10 and 100 ng/ml PMA inhibited (P < 0.05) PA activity. PA activity increased (P < 0.05) in POCC treated with up to 25 nM OA; however, activity decreased (P < 0.05) at concentrations > 75 nM. Treatment with 25 nM OA also induced the expression of an amiloride-sensitive PA (49-52 kD). Germinal vesicle breakdown and progression to metaphase II were inhibited (P < 0.05) by 2.5 mM dbcAMP and 2 mM 6-DMAP, whereas 100 ng/ml PMA and 25 nM OA inhibited (P < 0.05) only progression to metaphase II.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Reprod Dev 1995 Mar
PMID:Effects of stimulators of protein kinases A and C and modulators of phosphorylation on plasminogen activator activity in porcine oocyte-cumulus cell complexes during in vitro maturation. 777 47

Growth hormone-releasing factor (GRF) and vasoactive intestinal peptide (VIP) are two structurally homologous peptides sharing common target cell receptor and known to enhance FSH-induced steroidogenesis of undifferentiated granulosa cell in vitro. Although VIP, has been reported to stimulate plasminogen activator (PA) activity in rat granulosa cells, our knowledge on the actions and interactions of these two peptides with FSH in the regulation of rat granulosa cell PA system during follicular development remains incomplete. Undifferentiated and differentiated rat granulosa cells from pre-antral (DES-treated rats) and antral (eCG-treated rats) follicles, respectively, were cultured in a chemically defined medium in the absence and presence of FSH (400 ng/ml), GRF (10(-8)-10(-5) M) and/or VIP (10(-9)-10(-5) M). Net secreted (PAs) and cell-associated (PAc) PA activities was measured by the fibrinolysis assay and characterized by the fibrin overlay method. Granulosa cell differentiative (progestin secretion) and proliferative (DNA synthesis) responses were analyzed by radioimmunoassay and [3H]thymidine incorporation, respectively. Both GRF and VIP stimulated PAs and PAc activities in a concentration-dependent manner in 24-h cultures of granulosa cells from the two stages of follicular development. They (10(-5) M) enhanced FSH-stimulated PAs activity in granulosa cell cultures of pre-antral follicles, with GRF being more effective than VIP. On the contrary, only GRF (10 microM) potentiated FSH-induced PAs and PAc activities in cultures of granulosa cell from antral follicles. The stimulation of PA activity by these agonists decreased with the duration of culture irrespective of the stage of follicular development.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1995 Jan
PMID:Growth hormone releasing factor and vasoactive intestinal peptide stimulate rat granulosa cell plasminogen activator activity in vitro during follicular development. 779 29

Curli are fimbrial structures expressed by Escherichia coli that specifically interact with matrix proteins such as fibronectin and laminin. Similar structures are also expressed by Salmonella enteritidis and have been denoted thin aggregative fimbriae. Bacteria expressing curli and thin aggregative fimbriae were found to bind radiolabelled plasminogen as well as the tissue-type plasminogen activator (t-PA). By contrast, E. coli carrying a gene locus with an insertionally inactivated chromosomal curlin subunit were unable to bind the two human proteins. The purified subunit polypeptides of curli and thin aggregative fimbriae bound plasminogen and t-PA with high affinity (1 x 10(8) to 2 x 10(8) M-1). The binding of plasminogen and t-PA to curli-expressing E. coli was only partially inhibited by fibronectin and laminin. Plasminogen absorbed from human plasma by curli-expressing E. coli was readily converted to plasmin by t-PA; both plasmin and t-PA were functionally active when bound to the bacteria. A simultaneous binding of fibrinolytic proteins and matrix proteins to fimbriae of E. coli and S. enteritidis could provide these pathogens with both adhesive and invasive properties.
Mol Microbiol 1994 Nov
PMID:Plasminogen, absorbed by Escherichia coli expressing curli or by Salmonella enteritidis expressing thin aggregative fimbriae, can be activated by simultaneously captured tissue-type plasminogen activator (t-PA). 788 28

Proteolytic enzymes are required to mediate tumor cell invasion of adjacent tissues and spread of primary tumors to distant sites. Our objective was to examine the activities and molecular forms of plasminogen activator (PA) and matrix metalloproteases (MP) in primary and secondary growths of SC tumors of three human prostatic cell lines (Du-145, PC-3, and 1-LN-PC-3-1A [1-LN], a subline of PC-3) grown in nude mice. The plasminogen activator activities were 1.7 +/- 1.3 (+/- SD), 6.2 +/- 2.8, and 11.5 +/- 4.2 for Du-145, PC-3, and 1-LN in primary SC tumors, respectively. Urokinase was the predominant molecular form of PA found in each tumor as determined from its molecular size (predominantly 54 kDa with a minor activity of 33 kDa) and sensitivity to amiloride. Prominent MP activities of approximately 68, 76, and 96 kDa as well as lesser activities of about 56, 59, 63, 84, 165, and 180 kDa were found in 1-LN tumors, whereas only less active MP of 59, 68, and 96 kDa were detected in the parental PC-3 cells. Du-145 tumors expressed MP activities of 59 and 96 kDa. Treatment of 1-LN tumor extracts with p-aminophenylmercuric acetate (APMA) significantly reduced the MP activities of 76 and 165 kDa while increasing activities of 56, 59, 65, 68, and 84 kDa. The 76 and 165 kDa MP activities thus appear to be prominent proenzyme forms of MP expressed in the 1-LN tumor. Secondary growths of tumor were subsequently found near the site of initial injection of PC-3 and 1-LN cells following removal of the primary tumor. There was a 42% increase in PA activity in the PC-3 secondary tumors, but only an 8% increase in 1-LN secondary tumors. However, there was no difference in the activities or number of molecular forms of MP in extracts of PC-3 or 1-LN primary or secondary tumors. The substantial expression of MP activities in the more aggressive 1-LN subline of the human prostatic PC-3 cell line indicates that induction of certain MP may be an important regulatory event in prostate tumor progression.
Cell Mol Biol Res 1993
PMID:Plasminogen activator and metalloprotease activities of Du-145, PC-3, and 1-LN-PC-3-1A human prostate tumors grown in nude mice: correlation with tumor invasive behavior. 795 14

The solution structure of the kringle domain from urokinase-type plasminogen activator (u-PA) has been determined using 1H nuclear magnetic resonance spectroscopy and dynamical simulated annealing calculations. A total of 35 structures, 20 generated using a distance geometry method prior to simulated annealing and 15 generated using initial random phi, psi values, have been calculated based on 946 experimental nuclear Overhauser effect distance constraints and 48 dihedral angle constraints. Excluding the N- and C-terminal residues (-1 to 12, 77 to 82) and a number of surface residues (M18, G19, S42, D55 to R60, G67) that are disordered or flexible, the root mean square deviation values from the mean structure are 0.49(+/- 0.14) A and 0.65(+/- 0.16) A for the backbone atoms, and 1.03(+/- 0.21) A and 1.39(+/- 0.24) A for all heavy atoms, for the two sets of structures, respectively. An extended binding site for anionic polysaccharides such as heparin has been located on a relatively flat facet of the molecule, involving three consecutive arginines, R57, R58 and R60 (there is a deletion at site 59 of the consensus sequence), which form a cationic triad facing the solvent, and two histidines, H37 and H40, at the opposite end of the molecule. Comparison between the u-PA kringle structure and the crystal and NMR solution structures of tissue-type plasminogen activator kringle 2 has shown that the two proteins have similar global folds but demonstrate a number of local differences.
J Mol Biol 1994 Feb 04
PMID:Solution structure of the kringle domain from urokinase-type plasminogen activator. 810 91

The plasminogen activator (PA) system is present in the ovary and appears to be involved both in follicular growth and ovulation. Similarly, the growth hormone (GH) has been demonstrated to positively affect some ovarian activities. Interestingly, GH appears not only as a mediator of gonadotropin effects, but also as having an independent action of its own on the ovary. In the present study we wanted to investigate if GH could affect ovarian plasminogen activator (PA) activity and steroidogenesis. Granulosa cells from immature rats, injected with pregnant mare serum gonadotropin (PMSG) for inducing follicular growth, were cultured for 24 h with increasing concentrations of GH. A significant dose-dependent increase in tPA activity was observed in the GH-treated cells. This effect was exerted at the mRNA level and the use of cycloheximide, a protein synthesis inhibitor, suggested that GH did not require any other intermediary protein for inducing tPA-mRNA. Furthermore, cAMP levels were not affected by GH treatment. Finally, GH was found to increase progesterone (P) synthesis by granulosa cells. The correlation between the PA system and ovulation and the importance of a normal steroidogenesis for the ovarian physiology claim for a key role of GH in the ovarian activities.
Mol Cell Endocrinol 1994 Mar
PMID:Growth hormone induction of rat granulosa cell tissue-plasminogen activator expression and progesterone synthesis. 820 22

During angiogenesis capillary endothelial cells undergo a coordinated set of modifications in their interactions with extracellular matrix components. In this study we have investigated the effect of the prototypical angiogenic factor basic fibroblast growth factor (bFGF) on the expression and function of several integrins in microvascular endothelial cells. Immunoprecipitation experiments with antibodies to individual subunits indicated that microvascular cells express at their surface several integrins. These include the alpha 1 beta 1, alpha 2 beta 1, and alpha 3 beta 1 laminin/collagen receptors; the alpha 6 beta 1 laminin receptor; the alpha 5 beta 1 and alpha v beta 1 fibronectin receptors; the alpha 6 beta 4 basement membrane receptor; and the alpha v beta 3 and alpha v beta 5 vitronectin receptors. Treatment with bFGF caused a significant increase in the surface expression of the alpha 2 beta 1, alpha 3 beta 1, alpha 5 beta 1, alpha 6 beta 1, alpha 6 beta 4, and alpha v beta 5 integrins. In contrast, the level of expression of the alpha 1 beta 1 and alpha v beta 3 integrins was decreased in bFGF-treated cells. Immunoprecipitation of metabolically labeled cells indicated that bFGF increases the biosynthesis of the alpha 3, alpha 5, alpha 6, beta 4, and beta 5 subunits and decreases the production of the alpha v and beta 3 subunits. These results suggest that bFGF modulates integrin expression by altering the biosynthesis of individual alpha or beta subunits. In accordance with the upregulation of several integrins observed in bFGF-treated cells, these cells adhered better to fibronectin, laminin, vitronectin, and type I collagen than did untreated cells. The largest differences in beta 1 integrin expression occurred approximately 72 h after exposure to bFGF, at a time when the expression of the endothelial cell-to-cell adhesion molecule endoCAM was also significantly upregulated. In contrast, a shorter exposure to bFGF (24-48 h) was required for the maximal induction of plasminogen activator production in the same cells. Taken together, these results show that bFGF causes significant changes in the level of expression and function of several integrins in microvascular endothelial cells.
Mol Biol Cell 1993 Oct
PMID:Basic fibroblast growth factor modulates integrin expression in microvascular endothelial cells. 829 94

We have characterized tissue type plasminogen activator (tPA) promoter elements and nuclear factors required for follicle-stimulating hormone (FSH)-induced transcription of the rat tPA gene in granulosa cells and constitutive expression of the gene in the rat neuroblastoma cell line B103. Run-on transcription analysis of isolated nuclei revealed that B103 cells transcribe the tPA gene at a high and constitutive level, while FSH was found to induce tPA gene transcription in a rapid and transient manner in granulosa cells. The maximal FSH-induced transcription rate was obtained after 20 min and was similar in the absence or presence of the protein synthesis inhibitor cycloheximide. However, in the presence of cycloheximide, tPA transcription was not turned off but continued at a high rate for several hours. This phenomenon may at least partly explain the earlier finding that tPA mRNA is superinduced by FSH in the presence of cycloheximide. DNase I footprinting analysis of the first 621 bp of the tPA promoter revealed a total of six regions that interact with nuclear factors from B103 and granulosa cells. Deletion of the promoter region from positions -269 to -621, a region that includes the two most-upstream footprints, had no effect on constitutive or FSH-induced transcription in transient expression experiments. Nuclear extracts from both granulosa cells and B103 cells showed strong binding to a consensus cyclic AMP-responsive element (CRE) at positions -178 to -185 and a neighboring binding site for nuclear factor 1 (NF1) at positions -145 to -158. The factors binding to these two regions were identified as members of the CRE-binding protein and NF1 families of transcription factors, respectively. Footprints were also obtained over two GC boxes at positions -64 to -71 and -41 to -49. These footprints were more pronounced with nuclear extracts from B103 cells than with extracts from untreated or FSH-treated granulosa cells, but gel shift assays indicate that similar amounts of two distinct factors bind to the two GC boxes in both cell types. Transfection experiments using promoter constructs with inactivated promoter elements indicate that both the CRE and NF1 sites contribute to the FSH responsiveness of the rat tPA gene in granulosa cells, while only the NF1 site is important for constitutive expression in B103 cells. The two GC boxes were found to be necessary both for constitutive expression in B103 cells and for FSH-induced expression in granulosa cells, and inactivation of both GC boxes essentially eliminated the tPA promoter activity in both cell types.
Mol Cell Biol 1993 Jan
PMID:Transcriptional regulation of the rat tissue type plasminogen activator gene: localization of DNA elements and nuclear factors mediating constitutive and cyclic AMP-induced expression. 838 Feb 22

We established an immortalized cell line from endothelial cells derived from a human coronary artery, isolated at autopsy from 76-year-old male, by transfecting the cells with origin-minus simian virus 40 DNA. These cells showed SV40 T antigen in the nuclei and Ulex europaeus I agglutinin and factor VIII-related antigen, as endothelial cell markers, in their cytoplasm. This cell line synthesized prostacyclin, tissue-type plasminogen activator (tPA), and plasminogen activator inhibitor-1 (PAI-1) as well as produced the proform of matrix metalloproteinase 1, which was activated by cultivating the cells with plasminogen. These findings reveal that this immortalized endothelial cell line retains characteristics of human coronary endothelial cells, indicating that this cell line is useful for studying atherogenesis of the coronary artery.
Biochem Mol Biol Int 1995 Jul
PMID:Establishment and characterization of immortalized human coronary endothelial cells. 852 34


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