AJP - Lung Fuel your research with LabChart
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Am J Physiol Lung Cell Mol Physiol (February 21, 2003). doi:10.1152/ajplung.00178.2002
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
284/6/L1112    most recent
00178.2002v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Nabeyrat, E.
Right arrow Articles by Donnelly, L. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nabeyrat, E.
Right arrow Articles by Donnelly, L. E.
Submitted on June 6, 2002
Accepted on February 13, 2003

Mitogen-activated protein kinases mediate peroxynitrite-induced cell death in human bronchial epithelial cells

Elodie Nabeyrat1, Gina E. Jones1, Peter S. Fenwick1, Peter J. Barnes1, and Louise E. Donnelly1*

1 Department of Thoracic Medicine, National Heart and Lung Institute, Faculty of Medicine, Imperial College of Science, London, United Kingdom

* To whom correspondence should be addressed. E-mail: l.donnelly{at}ic.ac.uk.

Peroxynitrite, formed by the reaction of nitric oxide (NO.) with superoxide anions (O2.-), may play a role in the pathophysiology of inflammation. The effects of 3-morpholinosydnonimine (SIN-1), a peroxynitrite generator, on the human bronchial epithelial cell line BEAS-2B, were examined. SIN-1 exposure resulted in cell death in a time- and dose-dependent manner. Depletion of intracellular glutathione increased the vulnerability of the cells. Pre-treatment with MnTMPyP or hydroxocobalamin (HC), O2.- and NO. scavengers respectively, reduced significantly SIN-1-induced cell death (18.66±3.57 vs. 77.01±14.07 or 82.20±9.64, % cell viability SIN-1 vs. MnTMPyP or HC). Moreover, the mitogen-activated protein kinases (MAPK), p44/42 (ERK), p38 and p54/46 (JNK) were also activated in a time- and concentration-dependent manner. PD98059 and SB239063, specific inhibitors of ERK and p38 MAPK pathways, failed to protect cells against 1mM SIN-1. However, PD98059 partially inhibited (60% cell survival) SIN-1 effects at <= 0.25mM, and this was increased with the inclusion of SB239063. Therefore, MAPKs may mediate signal transduction pathways induced by peroxynitrite in lung epithelial cells leading to cell death.




This article has been cited by other articles:


Home page
 Physiol. Rev.Home page
P. Pacher, J. S. Beckman, and L. Liaudet
Nitric Oxide and Peroxynitrite in Health and Disease
Physiol Rev, January 1, 2007; 87(1): 315 - 424.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
R. A. Frost, G. J. Nystrom, and C. H. Lang
Lipopolysaccharide stimulates nitric oxide synthase-2 expression in murine skeletal muscle and C2C12 myoblasts via Toll-like receptor-4 and c-Jun NH2-terminal kinase pathways
Am J Physiol Cell Physiol, December 1, 2004; 287(6): C1605 - C1615.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
F. L. M. Ricciardolo, P. J. Sterk, B. Gaston, and G. Folkerts
Nitric Oxide in Health and Disease of the Respiratory System
Physiol Rev, July 1, 2004; 84(3): 731 - 765.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 2003 by the American Physiological Society.