Kidney lipids in galactosylceramide synthase-deficient mice. Absence of galactosylsulfatide and compensatory increase in more polar sulfoglycolipids

J Lipid Res. 2000 Aug;41(8):1237-43.

Abstract

UDP-galactose:ceramide galactosyltransferase (CGT) catalyzes the final step in the synthesis of galactosylceramide (GalCer). It has previously been shown that CGT-deficient mice do not synthesize GalCer and its sulfated derivative GalCer I(3)-sulfate (galactosylsulfatide, SM4s) but form myelin containing glucosylceramide (GlcCer) and sphingomyelin with 2-hydroxy fatty acids. Because relatively high concentrations of GalCer and SM4s are present also in mammalian kidney, we analyzed the composition of lipids in the kidney of Cgt(-/-) and, as a control, Cgt(+/-) and wild-type mice. The homozygous mutant mice lacked GalCer, galabiaosylceramide (Ga(2)Cer), and SM4s. Yet, they did not show any major morphological or functional defects in the kidney. A slight increase in GlcCer containing 4-hydroxysphinganine was evident among neutral glycolipids. Intriguingly, more polar sulfoglycolipids, that is, lactosylceramide II(3)-sulfate (SM3) and gangliotetraosylceramide II(3),IV(3)-bis-sulfate (SB1a), were expressed at 2 to 3 times the normal levels in Cgt(-/-) mice, indicating upregulation of biosynthesis of SB1a from GlcCer via SM3. Given that SM4s is a major polar glycolipid constituting renal tubular membrane, the increase in SM3 and SB1a in the mice deficient in CGT and thus SM4s appears to be a compensatory process, which could partly restore kidney function in the knockout mice.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Galactosylceramides / analysis*
  • Galactosylceramides / metabolism
  • Galactosyltransferases / deficiency*
  • Galactosyltransferases / genetics
  • Gangliosides / analysis
  • Glycolipids / analysis*
  • Glycolipids / metabolism
  • Kidney / chemistry*
  • Kidney / metabolism
  • Lipids / analysis*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • N-Acylsphingosine Galactosyltransferase
  • Phospholipids / analysis
  • Sulfates / analysis*
  • Sulfates / metabolism

Substances

  • Galactosylceramides
  • Gangliosides
  • Glycolipids
  • Lipids
  • Phospholipids
  • Sulfates
  • sulfoglycolipids
  • Galactosyltransferases
  • N-Acylsphingosine Galactosyltransferase