HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 293/2/C632    most recent 00137.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Nelin, L. D. Articles by Liu, Y. Search for Related Content PubMed PubMed Citation Articles by Nelin, L. D. Articles by Liu, Y.

RECEPTORS AND SIGNAL TRANSDUCTION

MKP-1 switches arginine metabolism from nitric oxide synthase to arginase following endotoxin challenge

Centers for ¹Perinatal Research and ²Gene Therapy, Columbus Children's Research Institute, Department of Pediatrics, The Ohio State University, Columbus, Ohio; and ³Department of Pediatrics, Children's Foundation Research Center at Le Bonheur Children's Medical Center, University of Tennessee Health Sciences Center at Memphis, Memphis, Tennessee

Submitted 26 March 2006 ; accepted in final form 17 April 2007

L-Arginine (L-arg) is metabolized to nitric oxide (NO) by inducible NO synthase (iNOS) or to urea and L-ornithine (L-orn) by arginase. NO is involved in the inflammatory response, whereas arginase is the first step in polyamine and proline synthesis necessary for tissue repair and wound healing. Mitogen-activated protein kinases (MAPK) mediate LPS-induced iNOS expression, and MAPK phosphatase-1 (MKP-1) plays a crucial role in limiting MAPK signaling in macrophages. We hypothesized that MKP-1, by attenuating iNOS expression, acts as a switch changing L-arg metabolism from NO production to L-orn production after endotoxin administration. To test this hypothesis, we performed studies in RAW264.7 macrophages stably transfected with an MKP-1 expression vector in thioglyollate-elicited peritoneal macrophages harvested from wild-type and Mkp-1^–/– mice, as well as in vivo in wild-type and Mkp-1^–/– mice. We found that overexpression of MKP-1 resulted in lower iNOS expression and NO production but greater urea production in response to LPS. Although deficiency of MKP-1 resulted in greater iNOS expression and NO production and lower urea production in response to LPS, neither the overexpression nor the deficiency of MKP-1 had any substantial effect on the expression of the arginases.

lung injury; macrophage; ornithine; mitogen-activated protein kinases

This article has been cited by other articles:

				R. Chang, L. G. Chicoine, H. Cui, N. L. Kanagy, B. R. Walker, Y. Liu, B. K. English, and L. D. Nelin Cytokine-induced arginase activity in pulmonary endothelial cells is dependent on Src family tyrosine kinase activity Am J Physiol Lung Cell Mol Physiol, October 1, 2008; 295(4): L688 - L697. [Abstract] [Full Text] [PDF]

				J. E. Hughes, S. Srinivasan, K. R. Lynch, R. L. Proia, P. Ferdek, and C. C. Hedrick Sphingosine-1-Phosphate Induces an Antiinflammatory Phenotype in Macrophages Circ. Res., April 25, 2008; 102(8): 950 - 958. [Abstract] [Full Text] [PDF]

				T. J. Calvert, L. G. Chicoine, Y. Liu, and L. D. Nelin Deficiency of mitogen-activated protein kinase phosphatase-1 results in iNOS-mediated hypotension in response to low-dose endotoxin Am J Physiol Heart Circ Physiol, April 1, 2008; 294(4): H1621 - H1629. [Abstract] [Full Text] [PDF]