help button home button
AJRCMB
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Published ahead of print on February 14, 2008, doi:10.1165/rcmb.2007-0371OC

Am. J. Respir. Cell Mol. Biol., Volume 39, Number 1, July 2008, 97-104

A more recent version of this article appeared on July 1, 2008
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
2007-0371OCv1
39/1/97    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
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
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Rinna, A.
Right arrow Articles by Forman, H. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rinna, A.
Right arrow Articles by Forman, H. J.

Submitted on October 13, 2007
Revised on February 14, 2008

SHP-1 Inhibition by 4-hydroxynonenal Activates Jun N-terminal Kinase and Glutamate Cysteine Ligase

Alessandra Rinna1 and Henry Jay Forman2*

1 University of California Merced, School of Natural Sciences, Merced, CA, USA; Department of Pharmacobiology, University of Messina, School of Pharmacy, Messina, Italy, 2 University of California Merced, School of Natural Sciences, Merced, CA, USA

* To whom correspondence should be addressed. E-mail: hjforman{at}gmail.com.

4-Hydroxy-2-nonenal (HNE) a major lipid peroxidation product is toxic at high concentrations but at near physiological concentrations, induces detoxifying enzymes. Previous data established that in human bronchial epithelial (HBE1) cells both genes for glutamate cysteine ligase (GCL) are induced by HNE through the JNK pathway. The protein-tyrosine phosphatase SHP-1 is thought to play a role as a negative regulator of cell signaling and has been implicated as such in the JNK pathway. In the present study, SHP-1 was demonstrated to contribute to HNE induced-gclc expression via regulation of the JNK pathway in HBE1 cells. Treatment of HBE1 cells with HNE induced phosphorylation of MKK4, JNK and c-Jun. HNE was able to inhibit PTP activity of SHP-1 through increased degradation of the protein. Furthermore transfection with siRNA SHP-1 showed an enhancement of JNK and c-Jun phosphorylation, but not of MKK4, leading to increased gclc expression. These results demonstrate that SHP-1 plays a role as a negative regulator of the JNK pathway and that HNE activated the JNK pathway by inhibiting SHP-1. Thus, SHP-1 acts as a sensor for HNE and is responsible for an important adaptive response to oxidative stress.




This article has been cited by other articles:


Home page
 J Gerontol A Biol Sci Med SciHome page
S. P. Singh, M. Niemczyk, D. Saini, V. Sadovov, L. Zimniak, and P. Zimniak
Disruption of the mGsta4 Gene Increases Life Span of C57BL Mice
J Gerontol A Biol Sci Med Sci, October 30, 2009; (2009) glp165v1.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
K. Bein, S. C. Wesselkamper, X. Liu, M. Dietsch, N. Majumder, V. J. Concel, M. Medvedovic, M. A. Sartor, L. N. Henning, C. Venditto, et al.
Surfactant-Associated Protein B Is Critical to Survival in Nickel-Induced Injury in Mice
Am. J. Respir. Cell Mol. Biol., August 1, 2009; 41(2): 226 - 236.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Proc. Am. Thorac. Soc. Am. J. Respir. Crit. Care Med.
Copyright © 2008 American Thoracic Society. 		  SOTA, FL