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)

Fetal rat osteoblast-enriched calvarial cells were used to study the effects of various growth factors and cytokines on plasminogen activator (PA) and plasminogen activator inhibitor (PAI) activities and the possible relationship of these effects to bone resorption. Confluent cultures were exposed to various factors under serum-free conditions, and levels of PA and PAI activities were examined in both conditioned medium (CM) and cell layer using the 125I-fibrin plate assay, fibrin zymogram, and reverse fibrin zymogram. According to the 125I-fibrin plate assay or zymogram, incubation of cells with acidic fibroblast growth factor (aFGF), basic FGF (bFGF), epidermal growth factor (EGF), and platelet-derived growth factor (PDGF) elevated the PA activity in the CM as well as in the cell layer extract. Incubation with interleukin 1 alpha (IL-1 alpha), tumor necrosis factor alpha (TNF alpha), and insulin-like growth factor I (IGF-I) produced no change in PA activity in either CM or cell layer. Addition of transforming growth factor beta (TGF beta) to calvarial cells resulted in nearly undetectable PA activity in CM with the fibrin plate assay but increased PA activity on the fibrin zymogram after PAI was separated from PA by SDS-PAGE. A reverse fibrin zymogram indicated that PAI activity was greatly enhanced in TGF beta-treated CM. TGF beta treatment also increased PA activity in the cell layer of calvarial cells. Treatment of calvarial cells with bFGF and PDGF slightly increased PAI secretion into medium. This increase, however, was not as dramatic as the increase of PA induced by these two agents. IL-1 alpha and TNF alpha did not change PAI concentration in CM. No detectable PAI activity was found in the cell layer in control and treated groups. The PA found in the CM and cell layer of rat calvarial cells was the urokinase type; the PAI stimulated by TGF beta was the endothelial cell type, PAI-1. The regulation of PA activity by growth factors and cytokines did not correlate with their resorption-stimulating activities. Thus, PA secreted by osteoblasts may not be the only factor involved in the initiation of bone resorption. Delineation of the function of PA and PAI in the physiology of bone tissue awaits further studies.
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PMID:Regulation of plasminogen activator and plasminogen activator inhibitor production by growth factors and cytokines in rat calvarial cells. 172 49

The migration of retinal pigment epithelial (RPE) cells from their normal anatomic position to a new position in the vitreous cavity is a critical feature of proliferative vitreous retinopathy. To determine if insulin-like growth factor I (IGF I), which is present in the vitreous fluid of diabetics, stimulates RPE cells, we examined the effects of IGF I on the proliferation, chemotaxis, and release of plasminogen activator by these cells. At the concentrations of IGF I tested, significant proliferation of RPE cells is seen. Significant chemotaxis of the RPE cells also is seen at all the concentrations of IGF I tested. The mean number of migrating cells per high-powered field in control studies was 43 +/- 13 (x +/- SEM), and for IGF I at 2.5 ng and 50 ng/ml the mean numbers of migrating cells were 96 +/- 17 and 483 +/- 62, respectively (P less than 0.001 for each comparison). The IGF I response was noted to be dose-dependent. The chemotactic response noted at 50 ng/ml of IGF I was greater than the positive chemotactic control of 10% fetal calf serum. Addition of alpha IR-3, an IGF I receptor antibody, eliminated the IGF I chemotactic response. The effect of IGF I on the secretion of plasminogen activators was assessed using an immunological assay for tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI). Media conditioned by RPE cells have measureable levels of PAI and t-PA antigen. IGF I supplementation resulted in an increase of t-PA secretion and PAI secretion over basal levels. These studies support a role for IGF I in modulating RPE cell function.
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PMID:Insulin-like growth factor I stimulates proliferation, migration, and plasminogen activator release by human retinal pigment epithelial cells. 211 Dec 35

This study was conducted to evaluate the effects of several growth factors on plasminogen activator (PA) activity in granulosa and theca cells collected from the largest preovulatory follicle in the hen ovary and to determine the involvement of cyclic adenosine monophosphate (cAMP) or protein kinase C, or both, in mediating the actions of epidermal growth factor (EGF) on granulosa PA activity. The granulosa cells were treated with increasing concentrations of: EGF (.33 to 16.4 nM); insulin-like growth factor I (IGF-I, 2.61 to 131 nM); fibroblast growth factor (FGF, .15 to 7.5 nM); or platelet-derived growth factor (PDGF, .02 to 1 nM). The treatments resulted in a dose-dependent increase in both cell-associated and secreted enzyme activity. The stimulatory effects of IGF-I (131 nM), however, were not mimicked with an equimolar concentration of the related peptide, insulin-like growth factor II. By contrast, theca cell PA activity was not significantly altered by EGF (16.4 nM), IGF-I (131 nM), FGF (7.5 nM), or PDGF (1 nM). Accumulation of cAMP was measured following exposure of granulosa cells to luteinizing hormone (LH, 10 ng, used as a positive control) or to EGF (16.4 and 164 nM) in the presence of .1 mM isobutylmethylxanthine. A 5-fold increase in cAMP levels was observed in response to LH; however, granulosa cell cAMP production was not altered by the presence of EGF.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of several growth factors on plasminogen activator activity in granulosa and theca cells of the domestic hen. 215 51

Using an in vitro system of pig Leydig cells (LC) and Sertoli cells (SC) we have demonstrated that: 1) LC contained specific receptors for both somatomedin-C/insulin-like growth factor I (Sm-C/IGF-I) and insulin, whereas SC contained only Sm-C/IGF-I receptors; 2) pretreatment of LC with insulin or Sm-C/IGF-I increased hCG receptor number and the cAMP and testosterone responses to this hormone. The enhanced steroidogenic capacity was related to an increased activity of several enzymes of the steroidogenic pathway. At physiological concentrations Sm-C/IGF-I was more potent than insulin, but the effects of the latter peptide at micromolar concentrations were similar to those produced by nanomolar concentrations of Sm-C/IGF-I. However, at maximal concentrations of both peptides, there was no additive effect; 3) the specificity of the effect of Sm-C/IGF-I was proven by the fact that all the effects induced by this peptide, but not by insulin, were blunted by an anti-Sm-C/IGF-I antibody; 4) pretreatment of SC with Sm-C/IGF-I at nM concentrations or with insulin (but only at microM concentrations) enhanced the stimulatory effect of FSH on cAMP production and the secretion of plasminogen activator; 5) in both LH and SC, Sm-C/IGF-I had small mitogenic effects but potentiated the mitogenic action of fibroblast growth factor (FGF). The effect of insulin was observed only at microM concentrations; 6) SC secreted a factor which had physico-chemical and biological properties similar to that of Sm-C/IGF-I. The secretion of this factor was stimulated by FGF and EGF.
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PMID:Differentiating effects of somatomedin-C/insulin-like growth factor I and insulin on Leydig and Sertoli cell functions. 285 90

Spatiotemporal release of growth factors from a delivery device can profoundly affect the efficacy of bone growth induction. Here, we report on a delivery platform based on the encapsulation of insulin-like growth factor I (IGF-I) in different poly(D,L-lactide) (PLA) and poly(D,L-lactide-co-glycolide) (PLGA) microsphere (MS) formulations to control IGF-I release kinetics. In vitro IGF-I release profiles generally exhibited an initial burst (14-36% of total IGF-I content), which was followed by a more or less pronounced dormant phase with little release (2 to 34 days), and finally, a third phase of re-increased IGF-I release. The osteoinductive potential of these different IGF-I PL(G)A MS formulations was tested in studies using 8-mm metaphyseal drill hole bone defects in sheep. Histomorphometric analysis at 3 and 6 weeks after surgery showed that new bone formation was improved in the defects locally treated with IGF-I PL(G)A MS (n=5) as compared to defects filled with IGF-I-free PL(G)A MS (n=4). The extent of new bone formation was affected by the particular release kinetics, although a definitive relationship was not evident. Local administration of IGF-I resulted in down-regulation of inflammatory marker genes in all IGF-I treated defects. The over-expression of growth factor genes in response to IGF-I delivery was restricted to formulations that produced osteogenic responses. These experiments demonstrate the osteoinductive potential of sustained IGF-I delivery and show the importance of delivery kinetics for successful IGF-I-based therapies.
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PMID:Impact of IGF-I release kinetics on bone healing: a preliminary study in sheep. 2395 21