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

Toxicological Sciences : an Official Journal of the Society of Toxicology
Cang-Bao XuLars Edvinsson

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 (dimethylsulfoxide-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 signaling was studied with Western blotting and phosphoELISA; this revealed that DSP induced extracellular-regulated protein kinases 1 and 2 (ERK1/2), p38, and nuclear factor-kappaB (NF-kappaB) phosphorylation within 3 h. Blocking ERK1/2, p38, or NF-kappaB activation by their specific inhibitors significantly attenuated the DSP-induced upregulation of ET(B) receptor-mediated contraction and both ET(B) receptor mRNA and protein expression. In addition, dexamethasone abolished the DSP-induce...Continue Reading

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Citations

Mar 19, 2014·Cell Biology and Toxicology·Wasana K SumanasekeraGregg D Rokosh
Nov 19, 2013·Acta Neuropathologica·Raymond Chuen-Chung ChangHo-Keung Ng
Oct 27, 2015·Toxicological Sciences : an Official Journal of the Society of Toxicology·Xue XiaoYong-xiao Cao
Jun 16, 2010·Pharmacology & Therapeutics·Cang-Bao XuLars Edvinsson
Jul 3, 2013·Basic & Clinical Pharmacology & Toxicology·Jian-Pu ZhengWen Peng
Oct 29, 2015·Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco·Kristian Agmund HaanesLars Edvinsson
Oct 11, 2014·Diabetes Research and Clinical Practice·Jason A HarmerUNKNOWN FIELD Vascular Study Investigators
Jan 15, 2013·Mediators of Inflammation·Nohra ChalouhiAaron S Dumont
Jan 15, 2014·Journal of Molecular and Cellular Cardiology·Denise LauStephan Baldus
Sep 7, 2016·Vascular Pharmacology·Yulong ChenYaping Zhang
May 12, 2011·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Lars I H Edvinsson, Gro Klitgaard Povlsen
May 8, 2019·Biological & Pharmaceutical Bulletin·Min JiaCang-Bao Xu

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