Abstract:
:Thrombin stimulates synthesis and secretion of endothelin-1 (ET-1), a vasoactive peptide that triggers responses in the vascular endothelium and smooth muscle. We investigated the signal transduction pathways by which thrombin stimulates preproET-1 gene expression and ET-1 peptide secretion in macrovascular cells (human umbilical vein endothelial cells [HUVECs] and bovine pulmonary artery endothelial cells [BPAECs]) and microvascular cells (human microvascular endothelial cell line [HMEC-1]). Thrombin (4 U/mL) stimulated maximal induction of ET-1 peptide secretion and preproET-1 mRNA after 2 hours in HUVECs and BPAECs and after 1 hour in HMEC-1. A synthetic thrombin receptor activator peptide confirmed ligand-specific receptor actions to induce preproET-1 mRNA. Protein kinase C (PKC) activation by phorbol ester transiently induced preproET-1 mRNA but had no effect on ET-1 peptide synthesis. PKC inhibitors sangivamycin and calphostin C and PKC depletion failed to suppress thrombin-stimulated preproET-1 mRNA. Adenylate cyclase and cAMP-dependent protein kinase did not participate in thrombin-induced preproET-1 gene activation. Thrombin stimulated a rapid increase in phosphotyrosine-containing proteins, suggesting a role for tyrosine phosphorylation in thrombin signaling. These data demonstrate that thrombin induces the preproET-1 gene and ET-1 peptide synthesis by a PKC-independent PTK-dependent pathway in macrovascular and microvascular endothelial cells. Protein tyrosine kinase inhibitors herbimycin A and genistein blocked thrombin-stimulated preproET-1 mRNA and peptide secretion, whereas daidzein, which lacks inhibitory activity, did not suppress thrombin-induced ET-1.
journal_name
Circ Resjournal_title
Circulation researchauthors
Marsen TA,Simonson MS,Dunn MJdoi
10.1161/01.res.76.6.987subject
Has Abstractpub_date
1995-06-01 00:00:00pages
987-95issue
6eissn
0009-7330issn
1524-4571journal_volume
76pub_type
杂志文章abstract::The aging population is increasing in developed countries. Because the incidence of cardiac disease increases dramatically with age, it is important to understand the molecular mechanisms through which the heart becomes either more or less susceptible to stress. Cardiac aging is characterized by the presence of hypert...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.116.307474
更新日期:2016-05-13 00:00:00
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pub_type: 杂志文章,评审
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pub_type: 杂志文章,评审
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pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.109.206631
更新日期:2010-03-05 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000089255.37804.72
更新日期:2003-08-22 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
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更新日期:2008-06-20 00:00:00
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pub_type: 杂志文章
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更新日期:1997-02-01 00:00:00
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pub_type: 杂志文章
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更新日期:1994-04-01 00:00:00
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pub_type: 杂志文章
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更新日期:2004-02-20 00:00:00
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pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.109.213314
更新日期:2010-05-14 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.117.305925
更新日期:2015-07-31 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.66.4.986
更新日期:1990-04-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.71.4.870
更新日期:1992-10-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:
更新日期:1997-04-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000133247.69803.c3
更新日期:2004-07-09 00:00:00
abstract::The aim was to identify energy-consuming processes, other than contraction, downregulated during moderate hypoxia ( approximately 5 micromol/L, 0.5% O(2)) and severe hypoxia (<0.5 micromol/L, <0.05% O(2)) in isolated neonatal cardiomyocytes. The metabolic response of cardiomyocytes to moderate and severe hypoxia was a...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.0000015592.95986.03
更新日期:2002-04-19 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.66.5.1184
更新日期:1990-05-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.53.2.274
更新日期:1983-08-01 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2006-04-28 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000141528.54850.bd
更新日期:2004-09-17 00:00:00
abstract::The consequences of endothelin receptor activation were examined in atrial tumor myocytes derived from transgenic mice (AT-1 cells). Endothelin-1 (endothelin) stimulates phosphoinositide hydrolysis in a dose-dependent manner. Endothelin also induces the rapid and transient translocation of protein kinase C (PKC)-epsil...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.78.4.724
更新日期:1996-04-01 00:00:00
abstract::Inducible nitric oxide synthase (iNOS) protein is expressed in cardiac myocytes of patients and experimental animals with congestive heart failure (CHF). Here we show that iNOS expression plays a role in pressure overload-induced myocardial chamber dilation and hypertrophy. In wild-type mice, chronic transverse aortic...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000264081.78659.45
更新日期:2007-04-13 00:00:00
abstract::Our objective was to test the hypotheses that 1) myoplasmic [Ca2+] is the primary determinant of crossbridge phosphorylation and that 2) phosphorylation is the primary determinant of crossbridge interactions with the thin filament in swine carotid arterial smooth muscle. We tested these hypotheses by evaluating the re...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.63.3.593
更新日期:1988-09-01 00:00:00
abstract::Although it has been established that myocyte enhancer factor 2 (MEF2) plays pivotal roles in the development of the cardiovascular system as well as skeletal muscle cells, little is known of its role in vascular inflammatory diseases such as atherosclerosis and restenosis after angioplasty. To investigate the role of...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000134631.75684.4A
更新日期:2004-07-09 00:00:00
abstract::To determine the acute and chronic effects of static and dynamic exercise upon the cardiovascular system, two groups of athletes were studied and compared to untrained control individuals. Thus, 12 long distance runners (LDR) and 17 competitive weight lifters (CWL) were compared to 10 light controls (LC) and 14 heavy ...
journal_title:Circulation research
pub_type: 杂志文章
doi:
更新日期:1981-06-01 00:00:00
abstract::Urea transporters have been cloned from kidney medulla (UT-A) and erythrocytes (UT-B). We determined whether UT-A proteins could be detected in heart and whether their abundance was altered by uremia or hypertension or in human heart failure. In normal rat heart, bands were detected at 56, 51, and 39 kDa. In uremic ra...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/hh1401.093293
更新日期:2001-07-20 00:00:00
abstract:RATIONALE:Cardiac myocyte-specific deletion of either glycogen synthase kinase (GSK)-3α and GSK-3β leads to cardiac protection after myocardial infarction, suggesting that deletion of both isoforms may provide synergistic protection. This is an important consideration because of the fact that all GSK-3-targeted drugs, ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.116.308544
更新日期:2016-04-15 00:00:00