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

Subroto Chatterjee, Wan Y. Shi, Patricia Wilson, Avi Mazumdar

Research output: Contribution to journalArticlepeer-review

Abstract

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 μM) derived from PKD exerted a 4-fold stimulation in the proliferation of these cells. However, at a concentration of 40 μM, 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 tarry acids (C16:0- C18:0). Lactosylceramide, but not glucosyl-ceramide 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 lactosyl-ceramide present in the PKD kidney may stimulate cell proliteration via activation of the p44 MAPK, and contribute to the pathophysiology in this disease.

Original languageEnglish (US)
Pages (from-to)1334-1344
Number of pages11
JournalJournal of Lipid Research
Volume37
Issue number6
StatePublished - Jun 1996

Keywords

  • cpk mice
  • gas chromatography-mass spectrometry
  • lactosylceramide biosynthesis
  • tyrosine kinase

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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