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Receptor Upregulation and MAPK Activity in Arteries and Bronchi Following Secondhand Smoke Exposure

Cao, Lei LU (2013) In Lund University, Faculty of Medicine Doctoral Dissertation Series 2013:90.
Abstract
Cigarette smoking is a major risk factor for cardiovascular and respiratory diseases. Contractile receptor changes have been observed in several vascular diseases. The intracellular mitogen activated protein kinase (MAPK) signaling pathways are suggested to be associated with receptor upregulation. The present study therefore aimed to investigate the status of vascular and bronchial receptor changes after secondhand smoke (SHS) exposure, focusing on the involvement of Raf/MEK/ERK1/2 signaling. The results show that upregulation of 5-hydroxytryptamine type 1B (5-HT1B) receptors and endothelin type A (ETA) receptors was found in rat cerebral arteries after exposure to SHS. SHS exposure modified the expression of ETB and ETA receptors in... (More)
Cigarette smoking is a major risk factor for cardiovascular and respiratory diseases. Contractile receptor changes have been observed in several vascular diseases. The intracellular mitogen activated protein kinase (MAPK) signaling pathways are suggested to be associated with receptor upregulation. The present study therefore aimed to investigate the status of vascular and bronchial receptor changes after secondhand smoke (SHS) exposure, focusing on the involvement of Raf/MEK/ERK1/2 signaling. The results show that upregulation of 5-hydroxytryptamine type 1B (5-HT1B) receptors and endothelin type A (ETA) receptors was found in rat cerebral arteries after exposure to SHS. SHS exposure modified the expression of ETB and ETA receptors in coronary arteries via the Raf/ERK/MAPK pathway. The SHS exposure-induced bronchial hyperreactivity was manifested by transcriptional upregulation of ETB, ETA and 5-HT2A receptors in bronchioles. The receptor upregulation includes the increased contractile characteristic response to the receptor agonists, elevated expression level of mRNA and/or protein for the contractile receptors. The mechanism study involves the protein phosphorylation analysis of Raf/ERK1/2 and inhibition of Raf-1 or MEK1/2 in vivo. The results show that SHS exposure induced Raf/ERK1/2 activation. Treatment together with SHS exposure showed the preventive effect of GW5074 on the SHS-induced receptor upregulation. After the first 8 weeks exposure, the receptor expression and its contractile function were significantly increased. However, the increased receptor expressions were normalized by accompanying of U0126 administration. Our knowledge of the Raf/MEK/ERK1/2 signaling pathway in SHS exposure-induced contractile receptor upregulation may provide a new therapeutic target for treatment of SHS-associated diseases. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Professor Møller, Peter, Department of Public Health, University of Copenhagen, Copenhagen, Denmark
organization
publishing date
type
Thesis
publication status
published
subject
keywords
coronary arteries, cerebral arteries, 5-hydroxytryptamine receptor, endothelin receptor, secondhand smoke exposure, bronchi
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
volume
2013:90
pages
127 pages
publisher
Faculty of Medicine, Lund University
defense location
Segerfalksalen, Wallenberg Neuroscience Center, Sölvegatan 17, Lund, Sweden
defense date
2013-11-14 09:00
ISSN
1652-8220
ISBN
978-91-87449-62-8
language
English
LU publication?
yes
id
7e2fbdb2-f099-4408-8d6f-9266c8c0078a (old id 4121482)
alternative location
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0044170
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0033008
http://onlinelibrary.wiley.com/doi/10.1111/j.1748-1716.2012.02478.x/abstract;jsessionid=0C5F459FBD7AF5FB61B6DC18B63FB7D9.f02t01
http://www.biomedcentral.com/1471-2202/12/109
date added to LUP
2013-10-25 13:44:40
date last changed
2018-06-14 08:49:35
@phdthesis{7e2fbdb2-f099-4408-8d6f-9266c8c0078a,
  abstract     = {Cigarette smoking is a major risk factor for cardiovascular and respiratory diseases. Contractile receptor changes have been observed in several vascular diseases. The intracellular mitogen activated protein kinase (MAPK) signaling pathways are suggested to be associated with receptor upregulation. The present study therefore aimed to investigate the status of vascular and bronchial receptor changes after secondhand smoke (SHS) exposure, focusing on the involvement of Raf/MEK/ERK1/2 signaling. The results show that upregulation of 5-hydroxytryptamine type 1B (5-HT1B) receptors and endothelin type A (ETA) receptors was found in rat cerebral arteries after exposure to SHS. SHS exposure modified the expression of ETB and ETA receptors in coronary arteries via the Raf/ERK/MAPK pathway. The SHS exposure-induced bronchial hyperreactivity was manifested by transcriptional upregulation of ETB, ETA and 5-HT2A receptors in bronchioles. The receptor upregulation includes the increased contractile characteristic response to the receptor agonists, elevated expression level of mRNA and/or protein for the contractile receptors. The mechanism study involves the protein phosphorylation analysis of Raf/ERK1/2 and inhibition of Raf-1 or MEK1/2 in vivo. The results show that SHS exposure induced Raf/ERK1/2 activation. Treatment together with SHS exposure showed the preventive effect of GW5074 on the SHS-induced receptor upregulation. After the first 8 weeks exposure, the receptor expression and its contractile function were significantly increased. However, the increased receptor expressions were normalized by accompanying of U0126 administration. Our knowledge of the Raf/MEK/ERK1/2 signaling pathway in SHS exposure-induced contractile receptor upregulation may provide a new therapeutic target for treatment of SHS-associated diseases.},
  author       = {Cao, Lei},
  isbn         = {978-91-87449-62-8},
  issn         = {1652-8220},
  keyword      = {coronary arteries,cerebral arteries,5-hydroxytryptamine receptor,endothelin receptor,secondhand smoke exposure,bronchi},
  language     = {eng},
  pages        = {127},
  publisher    = {Faculty of Medicine, Lund University},
  school       = {Lund University},
  series       = {Lund University, Faculty of Medicine Doctoral Dissertation Series},
  title        = {Receptor Upregulation and MAPK Activity in Arteries and Bronchi Following Secondhand Smoke Exposure},
  volume       = {2013:90},
  year         = {2013},
}