Kidney lipids in galactosylceramide synthase-deficient mice. Absence of galactosylsulfatide and compensatory increase in more polar sulfoglycolipids.
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.
Tadano-Aritomi
K
K
Department of Biochemistry, Teikyo University School of Medicine, Tokyo 173-8605, Japan.
Hikita
T
T
Fujimoto
H
H
Suzuki
K
K
Motegi
K
K
Ishizuka
I
I
D000818:Animals; D005699:Galactosylceramides / Q000032:analysis* / Q000378:metabolism; D005700:Galactosyltransferases / Q000172:deficiency* / Q000235:genetics; D005732:Gangliosides / Q000032:analysis; D006017:Glycolipids / Q000032:analysis* / Q000378:metabolism; D007668:Kidney / Q000737:chemistry* / Q000378:metabolism; D008055:Lipids / Q000032:analysis*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D051146:N-Acylsphingosine Galactosyltransferase; D010743:Phospholipids / Q000032:analysis; D013431:Sulfates / Q000032:analysis* / Q000378:metabolism
D005699:Galactosylceramides; D005732:Gangliosides; D006017:Glycolipids; D008055:Lipids; D010743:Phospholipids; D013431:Sulfates; C011117:sulfoglycolipids; D005700:Galactosyltransferases; D051146:N-Acylsphingosine Galactosyltransferase