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Titolo:
Ethanol-induced up-regulation of the urokinase receptor in cultured human endothelial cells
Autore:
Tabengwa, EM; Grenett, HE; Benza, RL; Abou-Agag, LH; Tresnak, JK; Wheeler, CG; Booyse, FM;
Indirizzi:
Univ Alabama, Dept Med, Div Cardiovasc Dis, Birmingham, AL 35294 USA Univ Alabama Birmingham AL USA 35294 iovasc Dis, Birmingham, AL 35294 USA
Titolo Testata:
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
fascicolo: 2, volume: 25, anno: 2001,
pagine: 163 - 170
SICI:
0145-6008(200102)25:2<163:EUOTUR>2.0.ZU;2-F
Fonte:
ISI
Lingua:
ENG
Soggetto:
PLASMINOGEN-ACTIVATOR RECEPTOR; SURFACE-LOCALIZED FIBRINOLYSIS; HSC70 GENE-TRANSCRIPTION; HYPERTRIGLYCERIDEMIC VLDL; PROTEIN-KINASE; MESSENGER-RNA; PAI-1 GENE; EXPRESSION; ALCOHOL; BINDING;
Keywords:
endothelial cells; urokinase plasminogen activator receptor; fibrinolysis; ethanol;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
56
Recensione:
Indirizzi per estratti:
Indirizzo: Tabengwa, EM 1530 3rd Ave S,BBRB 809, Birmingham, AL 35294 USA 1530 3rd Ave S,BBRB 809 Birmingham AL USA 35294 AL 35294 USA
Citazione:
E.M. Tabengwa et al., "Ethanol-induced up-regulation of the urokinase receptor in cultured human endothelial cells", ALC CLIN EX, 25(2), 2001, pp. 163-170

Abstract

Background: Moderate alcohol consumption has been correlated to reduced coronary artery disease (CAD) risk and mortality. This alcohol effect may be mediated in part by an increased endothelial cell (EC) fibrinolysis. ECs synthesize fibrinolytic proteins, tissue plasminogen activator (t-PA), urokinase type plasminogen activator (u-PA), and plasminogen activator inhibitor type-1(PAI-l). In addition, they synthesize and regulate receptors for fibrinolytic proteins, namely (t-PA and plasminogen receptor) Annexin II and u-PA receptor (u-PAR). These receptors play an important role in the regulated expression of receptor-bound plasminogen activator conversion of receptor-bound plasminogen to receptor-bound plasmin on the EC surface (surface-localized fibrinolytic activity). Therefore, systemic factors, such as ethanol, that affect the level, or activity or interaction of one or more of thesecomponents, resulting in the increased expression of surface-localized EC fibrinolytic activity, will be expected to reduce the risk for thrombosis, CAD, and myocardial infarction (MI). We have previously shown that low ethanol up-regulates t-PA and u-PA gene transcription, while it down-regulates PAI-1, hence resulting in increased (sustained, 24 hr) surface-localized ECfibrinolytic activity. The current studies were carried out to determine whether low ethanol increased u-PAR expression in cultured human umbilical cord vein ECs (HUVECs). Methods: Cultured HUVECs were preincubated (1 hr) in the absence/presence of ethanol (0.025- 0.2%, v/v); u-PAR mRNA (RT-PCR), antigen (western blot),and activity (I-125-u-PA ligand binding/Scatchard analysis) levels were then measured after 0-24 hr. To determine whether the ethanol-induced changesin the u-PAR expression were transcriptional, transient transfection studies were carried out using a u-PAR/ luciferase promoter construct (pu-PAR120/luc [1.2-kb u-PAR promoter fragment ligated to a promoterless luciferase vector]. Results: uPAR mRNA levels increased 2- to 3-fold and antigen levels (western blot) increased 2- to 4-fold while u-PA binding activity increased 36% (1.25 vs. 1.7 x 10(5) sites/cell, B-max) without significantly affecting theK-d (1-2 nM). Transient transfection of cultured HUVECs with a pu-PAR120/luc construct resulted in a 2- to 3-fold increase in promoter activity in ethanol-induced cultures, compared with controls. Conclusion: These combined results demonstrate that low ethanol (less thanor equal to0.1%, v/v) induces the upregulation of u-PAR gene transcription, resulting in increased u-PAR ligand binding activity. These results also further identify/define the contribution and role of another fibrinolytic protein in the overall ethanol-induced increase in surface-localized EC fibrinolysis that may underlie and contribute, in part, to the cardioprotectionattributed to moderate alcohol consumption.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 20/09/20 alle ore 23:43:03