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Lipid soluble smoke particles up-regulate vascular smooth muscle ETB receptors via activation of mitogen activating protein kinases and NF-kappaB pathways.

Xu, Cang-Bao LU ; Zheng, Jianpu LU ; Zhang, Wei; Zhang, Yaping LU and Edvinsson, Lars LU (2008) In Toxicological Sciences 106(2). p.546-555
Abstract
Cigarette smoke is a strong risk factor for cardiovascular disease. However, the underlying molecular mechanisms that lead to cigarette smoke-associated cardiovascular disease remain elusive. With functional and molecular methods, we demonstrate for the first time that lipid soluble cigarette smoke particles (DSP) increased the expression of endothelin type B (ET(B)) receptors in arterial smooth muscle cells. The increased ET(B) receptors in arterial smooth muscle cells was documented as enhanced contractility (sensitive myograph technique), elevated levels of ET(B) receptor mRNA (quantitative real-time PCR) and protein expressions (immunohistochemistry and Western blotting). Intracellular signalling was studied with Western blotting and... (More)
Cigarette smoke is a strong risk factor for cardiovascular disease. However, the underlying molecular mechanisms that lead to cigarette smoke-associated cardiovascular disease remain elusive. With functional and molecular methods, we demonstrate for the first time that lipid soluble cigarette smoke particles (DSP) increased the expression of endothelin type B (ET(B)) receptors in arterial smooth muscle cells. The increased ET(B) receptors in arterial smooth muscle cells was documented as enhanced contractility (sensitive myograph technique), elevated levels of ET(B) receptor mRNA (quantitative real-time PCR) and protein expressions (immunohistochemistry and Western blotting). Intracellular signalling was studied with Western blotting and phosphoELISA; this revealed that DSP induced extracellular-regulated protein kinase 1 and 2 (ERK1/2), p38 and nuclear factor-kappaB (NF-kappaB) phosphorylation within 3 hours. Blocking ERK1/2, p38 or NF-kappaB activation by their specific inhibitors significantly attenuated the DSP-induced up-regulation of ET(B) receptor-mediated contraction and both ET(B) receptor mRNA and protein expression. In addition, dexamethasone abolished the DSP-induced up-regulation of ET(B) receptor-mediated contraction. In conclusion, up-regulation of ET(B) receptors by DSP in arterial smooth muscle cells involves activation of mitogen activating protein kinases (ERK1/2 and p38) and the downstream transcriptional factor NF-kappaB pathways. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Toxicological Sciences
volume
106
issue
2
pages
546 - 555
publisher
Oxford University Press
external identifiers
  • wos:000260979800025
  • pmid:18718921
  • scopus:56649109924
ISSN
1096-0929
DOI
10.1093/toxsci/kfn173
language
English
LU publication?
yes
id
39d7452e-491f-4ebc-aa4d-4c9c135d512c (old id 1223015)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18718921?dopt=Abstract
date added to LUP
2008-09-02 15:14:05
date last changed
2017-03-26 03:46:48
@article{39d7452e-491f-4ebc-aa4d-4c9c135d512c,
  abstract     = {Cigarette smoke is a strong risk factor for cardiovascular disease. However, the underlying molecular mechanisms that lead to cigarette smoke-associated cardiovascular disease remain elusive. With functional and molecular methods, we demonstrate for the first time that lipid soluble cigarette smoke particles (DSP) increased the expression of endothelin type B (ET(B)) receptors in arterial smooth muscle cells. The increased ET(B) receptors in arterial smooth muscle cells was documented as enhanced contractility (sensitive myograph technique), elevated levels of ET(B) receptor mRNA (quantitative real-time PCR) and protein expressions (immunohistochemistry and Western blotting). Intracellular signalling was studied with Western blotting and phosphoELISA; this revealed that DSP induced extracellular-regulated protein kinase 1 and 2 (ERK1/2), p38 and nuclear factor-kappaB (NF-kappaB) phosphorylation within 3 hours. Blocking ERK1/2, p38 or NF-kappaB activation by their specific inhibitors significantly attenuated the DSP-induced up-regulation of ET(B) receptor-mediated contraction and both ET(B) receptor mRNA and protein expression. In addition, dexamethasone abolished the DSP-induced up-regulation of ET(B) receptor-mediated contraction. In conclusion, up-regulation of ET(B) receptors by DSP in arterial smooth muscle cells involves activation of mitogen activating protein kinases (ERK1/2 and p38) and the downstream transcriptional factor NF-kappaB pathways.},
  author       = {Xu, Cang-Bao and Zheng, Jianpu and Zhang, Wei and Zhang, Yaping and Edvinsson, Lars},
  issn         = {1096-0929},
  language     = {eng},
  number       = {2},
  pages        = {546--555},
  publisher    = {Oxford University Press},
  series       = {Toxicological Sciences},
  title        = {Lipid soluble smoke particles up-regulate vascular smooth muscle ETB receptors via activation of mitogen activating protein kinases and NF-kappaB pathways.},
  url          = {http://dx.doi.org/10.1093/toxsci/kfn173},
  volume       = {106},
  year         = {2008},
}