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

J. Biol. Chem., Vol. 277, Issue 15, 13321-13330, April 12, 2002

This Article Full Text Full Text (PDF) All Versions of this Article: 277/15/13321    most recent M108203200v1 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 PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chaturvedi, L. S. Articles by Koul, H. K. Search for Related Content PubMed PubMed Citation Articles by Chaturvedi, L. S. Articles by Koul, H. K. Social Bookmarking                      What's this?

Oxalate Selectively Activates p38 Mitogen-activated Protein Kinase and c-Jun N-terminal Kinase Signal Transduction Pathways in Renal Epithelial Cells^*

Lakshmi S. Chaturvedi, Sweaty Koul, Avtar Sekhon, Akshay Bhandari, Mani Menon, and Hari K. Koul^§

From the Biochemistry and Molecular Biology Laboratory, Vattikuti Urology Institute, Henry Ford Health Sciences Center, Detroit, Michigan 48202

Oxalate, a metabolic end product, is an important factor in the pathogenesis of renal stone disease. Oxalate exposure to renal epithelial cells results in re-initiation of the DNA synthesis, altered gene expression, and apoptosis, but the signaling pathways involved in these diverse effects have not been evaluated. The effects of oxalate on mitogen- and stress-activated protein kinase signaling pathways were studied in LLC-PK1 cells. Exposure to oxalate (1 mM) rapidly stimulated robust phosphorylation and activation of p38 MAPK. Oxalate exposure also induced modest activation of JNK, as monitored by phosphorylation of c-Jun. In contrast, oxalate exposure had no effect on phosphorylation and enzyme activity of p42/44 MAPK. We also show that specific inhibition of p38 MAPK by 4(4-(fluorophenyl)-2-(4-methylsulfonylphenyl)-5-(4-pyridyl)imidazole (SB203580) or by overexpression of a kinase-dead dominant negative mutant of p38 MAPK abolishes oxalate induced re-initiation of DNA synthesis in LLC-PK1 cells. The inhibition is dose-dependent and correlates with in situ activity of native p38 MAP kinase, determined as MAPK-activated protein kinase-2 activity in cell extracts. Thus, this study not only provides the first demonstration of selective activation of p38 MAPK and JNK signaling pathways by oxalate but also suggests that p38 MAPK activity is essential for the effects of oxalate on re-initiation of DNA synthesis.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				H. K. Koul, M. Menon, L. S. Chaturvedi, S. Koul, A. Sekhon, A. Bhandari, and M. Huang COM Crystals Activate the p38 Mitogen-activated Protein Kinase Signal Transduction Pathway in Renal Epithelial Cells J. Biol. Chem., September 20, 2002; 277(39): 36845 - 36852. [Abstract] [Full Text] [PDF]