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)

Ethanol and in a greater degree acetaldehyde inhibit activation of plasminogen evoked by urokinase and streptokinase. Ethanol does not inhibit the plasmin caseinolytic and fibrinolytic activities though the former inhibits amidolytic activity of the enzyme but only insignificantly. Acetaldehyde inhibits the plasmin activity towards casein, fibrin and H-D-Val-Leu-Lys-pNA.
 ...
PMID:[Inhibition by ethanol and acetaldehyde the plasmin activity and plasminogen activation induced by urokinase and streptokinase]. 297 11

The aim of this study was to investigate the effect of acetaldehyde on the activity and expression of urokinase type plasminogen activator gene in a clone of hepatic stellate cells. CFSC-2G cells showed typical morphological changes of the stellate cell activation, which were accompanied by an increase in the amount of collagen with all doses of acetaldehyde used. The treatment of the cells with doses of 100 and 175 micromol/l acetaldehyde, produced an increase in the urokinase type plasminogen activator activity not only in the cell extract, but also in conditioned medium. However, the use of higher doses of acetaldehyde (250 and 350 micromol/l) produced an inhibitory effect on the urokinase type plasminogen activator activity. In contrast, the higher urokinase type plasminogen activator gene expression was observed with doses of 175, 250, and 350 micromol/l. Our results shown that acetaldehyde induced changes in synthesis, release, and expression of urokinase type plasminogen activator in CFSC-2G cells. Those findings suggest that the alterations in the synthesis and expression of the urokinase type plasminogen activator might be another event associated to the activation of hepatic stellate cell after exposure to hepatotoxic agents like-acetaldehyde. The role of urokinase type plasminogen activator in fibrogenesis was analyzed.
 ...
PMID:Acetaldehyde increases the activity and gene expression of urokinase type plasminogen activator in a hepatic stellate cell line. 1051 95

Previous studies from our laboratory have shown that malondialdehyde-acetaldehyde-protein adducts (MAA adducts) are formed in hepatocytes of ethanol-fed rats and directly influence the hepatic stellate cells (HSCs) to induce their secretion of chemokines and to up-regulate their expression of adhesion molecules. Since protein kinase C (PKC) is known to play a major role in many diverse intracellular signal transduction processes, we investigated whether MAA adducts influence the function of HSCs via a PKC-dependent pathway. HSCs in culture were exposed to MAA adducts, and PKC activity was determined. We observed a time- and concentration-dependent activation of PKC when cultures were exposed to BSA-MAA as compared with unmodified BSA. Using PKC isoform-specific inhibitors, we also showed that BSA-MAA induces the activation of a specific isoform of PKC, PKC-alpha, in HSCs. No activation of PKC was observed when HSCs were exposed to other aldehyde adducts such as BSA-acetaldehyde or BSA-malondialdehyde, indicating that the effects of MAA adducts on HSCs were somewhat specific. We further examined whether the observed increase in PKC activation induced by MAA adducts in HSCs, in turn, causes a functional effect. We observed that BSA-MAA induces the increased secretion of urokinase-type plasminogen activator, a key component of the plasmin-generating system, and that PKC activation is necessary for this enhanced urokinase-type plasminogen activator secretion. These results indicate that MAA adducts via a PKC-mediated pathway may regulate plasmin-mediated matrix degradation in the liver, thereby contributing to the progression of hepatic fibrosis.
 ...
PMID:Effect of malondialdehyde-acetaldehyde-protein adducts on the protein kinase C-dependent secretion of urokinase-type plasminogen activator in hepatic stellate cells. 1185 6

The aim of this study was to determine whether transforming growth factor-beta1 (TGF-beta1) induces the synthesis, release and gene expression of urokinase-type plasminogen activator (uPA) in hepatic stellate cells. In addition to stimulating collagen production, TGF-beta1 induced the morphological and phenotypical changes characteristic of hepatic stellate cell activation. However, these changes accentuated in cells previously activated with acetaldehyde. TGF-beta1 increased to 2-fold uPA activity in lysates from quiescent cells, and to 3.5-fold in activated cells, and induced uPA gene expression to the same extent in both activated and non-activated cells. TGF-beta1 had a modest stimulatory action on the release of uPA into the conditioned medium, but reduced acetaldehyde-induced release, as demonstrated by Western blot analysis. In accord, whereas TGF-beta1 produces no effect on uPA activity in the conditioned media from quiescent cells, it significantly reduces the stimulatory action of acetaldehyde. These results show that the activity and gene expression of uPA are regulated by both acetaldehyde and TGF-beta1 and that the proteolytic activity in the extracellular space is reduced by the influence of TGF-beta1. Further studies on the molecular mechanisms responsible for the regulation of the plasminogen system by TGF-beta1 and other molecules in the presence of acetaldehyde will contribute to a better understanding of the processes involved in fibrogenesis.
 ...
PMID:Modulation of urokinase-type plasminogen activator by transforming growth factor beta1 in acetaldehyde-activated hepatic stellate cells. 1545 60