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

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services 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 Chatterjee, S. Articles by Mazumdar, A. Search for Related Content PubMed PubMed Citation Articles by Chatterjee, S. Articles by Mazumdar, A. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol 37, 1334-1344, Copyright © 1996 by Lipid Research, Inc.

ARTICLES

Role of lactosylceramide and MAP kinase in the proliferation of proximal tubular cells in human polycystic kidney disease

S Chatterjee, WY Shi, P Wilson and A Mazumdar
Department of Pediatrics, Johns Hopkins University, Baltimore, MD 21287- 3654, USA.

Polycystic kidney disease (PKD) is a common genetic disease characterized by the proliferation of epithelial cells, formation of cysts, and the progression of renal deficiency. We have investigated a possible role of glycosphingolipids in the proliferation of human kidney cells in this disease. The levels of glucosylceramide and lactosylceramide and the activity of glucosylceramide synthase (GlcT-1) and lactosylceramide synthase (GalT-2) were elevated 2-fold and 3-fold, respectively, in the PKD tissue compared to control. Lactosylceramide, but not glucosylceramide (10 microM) derived from PKD exerted a 4-fold stimulation in the proliferation of these cells. However, at a concentration of 40 microM, lactosylceramide and glucosylceramide both stimulated cell proliferation on the order of 10-fold and 2.5-fold, respectively, as compared to control. This phenomenon may be due to the enrichment of lactosylceramide containing shorter chain fatty acids (C16:0-C18:0). Lactosylceramide, but not glucosylceramide exerted a time-dependent stimulation in the phosphorylation of mitogen-activated protein kinase (p44 MAPK) in normal human kidney proximal tubular cells. Moreover, the kidneys and cultured cells from the PKD patients contained higher levels of the p44 MAPK as compared to normal human kidneys. In sum, our studies indicate that lactosylceramide present in the PKD kidney may stimulate cell proliferation via activation of the p44 MAPK, and contribute to the pathophysiology in this disease.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. Omori, M. Hida, H. Fujita, H. Takahashi, S. Tanimura, M. Kohno, and M. Awazu Extracellular Signal-Regulated Kinase Inhibition Slows Disease Progression in Mice with Polycystic Kidney Disease J. Am. Soc. Nephrol., June 1, 2006; 17(6): 1604 - 1614. [Abstract] [Full Text] [PDF]

				M. Rajesh, A. Kolmakova, and S. Chatterjee Novel Role of Lactosylceramide in Vascular Endothelial Growth Factor-Mediated Angiogenesis in Human Endothelial Cells Circ. Res., October 14, 2005; 97(8): 796 - 804. [Abstract] [Full Text] [PDF]

				P. D. Wilson Polycystic Kidney Disease N. Engl. J. Med., January 8, 2004; 350(2): 151 - 164. [Full Text] [PDF]

				F. A. Belibi, D. P. Wallace, T. Yamaguchi, M. Christensen, G. Reif, and J. J. Grantham The Effect of Caffeine on Renal Epithelial Cells from Patients with Autosomal Dominant Polycystic Kidney Disease J. Am. Soc. Nephrol., November 1, 2002; 13(11): 2723 - 2729. [Abstract] [Full Text] [PDF]

				C. M. Sorenson and N. Sheibani Sustained activation of MAPK/ERKs signaling pathway in cystic kidneys from bcl-2 -/- mice Am J Physiol Renal Physiol, November 1, 2002; 283(5): F1085 - F1090. [Abstract] [Full Text] [PDF]

				W. Tian, Z. Zhang, and D. M. Cohen MAPK signaling and the kidney Am J Physiol Renal Physiol, October 1, 2000; 279(4): F593 - F604. [Abstract] [Full Text] [PDF]

				G. Gabriëls, A. Werners, S. Mauss, and J. Greven Evidence for Differential Regulation of Renal Proximal Tubular p-Aminohippurate and Sodium-Dependent Dicarboxylate Transport J. Pharmacol. Exp. Ther., August 1, 1999; 290(2): 710 - 715. [Abstract] [Full Text]

				A. K. Bhunia, T. Arai, G. Bulkley, and S. Chatterjee Lactosylceramide Mediates Tumor Necrosis Factor-alpha -induced Intercellular Adhesion Molecule-1 (ICAM-1) Expression and the Adhesion of Neutrophil in Human Umbilical Vein Endothelial Cells J. Biol. Chem., December 18, 1998; 273(51): 34349 - 34357. [Abstract] [Full Text] [PDF]

				S. Chatterjee Sphingolipids in Atherosclerosis and Vascular Biology Arterioscler. Thromb. Vasc. Biol., October 1, 1998; 18(10): 1523 - 1533. [Abstract] [Full Text] [PDF]

				A. K. Bhunia, H. Han, A. Snowden, and S. Chatterjee Redox-regulated Signaling by Lactosylceramide in the Proliferation of Human Aortic Smooth Muscle Cells J. Biol. Chem., June 20, 1997; 272(25): 15642 - 15649. [Abstract] [Full Text] [PDF]