Journal of Lipid Research, Vol 35, 1611-1618, Copyright © 1994 by Lipid Research, Inc.

ARTICLES

Abnormalities of glycosphingolipid, sulfatide, and ceramide in the polycystic (cpk/cpk) mouse

GD Deshmukh, NS Radin, VH Gattone 2nd and JA Shayman
Department of Internal Medicine, University of Michigan, Ann Arbor 48109-0676.

Polycystic kidney disease is a disorder marked by aberrant renal tubular epithelial cell proliferation and transport abnormalities. Sphingolipids are ubiquitous membrane components implicated in several cellular functions including cell membrane sorting, signaling, growth, ion transport, and adhesion. To investigate a potential pathogenic role for sphingolipids in cystic kidney disease, we studied the sphingolipid content and associated enzymatic activities of the kidneys from cpk/cpk mice and their phenotypically normal litter mates. The neutral glycolipids, including glucosylceramide and lactosylceramide, displayed a striking increase in 3-week-old cpk/cpk mice as did the acidic lipid, ganglioside GM3. However, a correspondingly significant decrease in sulfoglycolipid and ceramide concentration was observed in the cpk/cpk kidneys. Glucosylceramide synthase activity was higher in the kidneys of the cpk/cpk mice than in those of the controls. Kinetic analysis of the glucosylceramide synthase revealed the presence of an endogenous activator in the cystic kidney. A marked decrease in sulfotransferase activity was observed in both whole kidney homogenates and in microsomal preparations that was consistent with the decrement in sulfolipid content. The increase in GM3, glucosyl- and lactosylceramide may therefore be the result of impaired sulfolipid synthesis at the 3- week time point. While sulfolipid and glucosylceramide concentrations are not different at 1 and 2 weeks of age, ceramide concentrations in cystic kidneys are significantly reduced compared to kidneys from phenotypically normal mice. These results suggest that sphingolipids may play a potential role in the proliferative and transport abnormalities associated with cystic renal disease and the development of azotemia.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				J. Matsuda, M. Kido, K. Tadano-Aritomi, I. Ishizuka, K. Tominaga, K. Toida, E. Takeda, K. Suzuki, and Y. Kuroda Mutation in saposin D domain of sphingolipid activator protein gene causes urinary system defects and cerebellar Purkinje cell degeneration with accumulation of hydroxy fatty acid-containing ceramide in mouse Hum. Mol. Genet., November 1, 2004; 13(21): 2709 - 2723. [Abstract] [Full Text] [PDF]

				F.-L. Chi, Y.-S. Yuan, S.-Y. Wang, and Z.-M. Wang Study on Ceramide Expression and DNA Content in Patients With Healthy Mucosa, Leukoplakia, and Carcinoma of the Larynx Arch Otolaryngol Head Neck Surg, March 1, 2004; 130(3): 307 - 310. [Abstract] [Full Text] [PDF]

				L. M. Guay-Woodford Murine models of polycystic kidney disease: molecular and therapeutic insights Am J Physiol Renal Physiol, December 1, 2003; 285(6): F1034 - F1049. [Abstract] [Full Text] [PDF]

				K. Tadano-Aritomi, T. Hikita, A. Suzuki, H. Toyoda, T. Toida, T. Imanari, and I. Ishizuka Determination of lipid-bound sulfate by ion chromatography and its application to quantification of sulfolipids from kidneys of various mammalian species J. Lipid Res., October 1, 2001; 42(10): 1604 - 1608. [Abstract] [Full Text] [PDF]

				R. A. Memon, W. M. Holleran, Y. Uchida, A. H. Moser, C. Grunfeld, and K. R. Feingold Regulation of sphingolipid and glycosphingolipid metabolism in extrahepatic tissues by endotoxin J. Lipid Res., March 1, 2001; 42(3): 452 - 459. [Abstract] [Full Text]

				R. A. Memon, W. M. Holleran, Y. Uchida, A. H. Moser, S. Ichikawa, Y. Hirabayashi, C. Grunfeld, and K. R. Feingold Regulation of Glycosphingolipid Metabolism in Liver during the Acute Phase Response J. Biol. Chem., July 9, 1999; 274(28): 19707 - 19713. [Abstract] [Full Text] [PDF]