engleski

Expression of neutral glycosphingolipids in the brain and spleen of mice lacking TNF receptor 1

We found different expression of neutral glycosphingolipids (GSLs) in the brain and spleen of mice lacking the gene for the tumor necrosis factor-a receptor p55 (TNFR1). Neutral GSLs of the ganglio-, globo-, and neolacto-series were determined in the tissues of homozygous (TNFR1-/-) and heterozygous (TNFR1+/-) animals by high perfomance thin layer chromatography (HPTLC) overlay immunostaining with specific antibodies. The spleen of homozygous TNFR1 knockout mice lacked glucosylceramide substituted with palmitic acid, GlcCer(C16) and showed severe reduction in the expression of GlcCer(C16). In addition, gangliotetraosylceramide, Gg4Cer, substituted with palmitic acid, Gg4Cer(C24), and globotetraosylceramide, Gb4Cer, were down-regulated in TNFR1-/- spleen in comparison with heterozygous control. The brain of both groups of animals (TNFR1-/- and TNFR1+/-) did not express detectable levels of Gg4Cer, Gb5Cer and Gb4Cer, but the brain of TNFR1 knockout mice expressed abundant globotriaosylceramide, Gb3Cer, compared to no expression in control heterozygous mice. nLcCer(C24) was slightly higher expressed in the brain of TNFR1-/- mice compared to control animals. This study provides in vivo evidence that TNF signaling via the TNFR1 is involved in the acquisition of a distinct GSL assembly in the brain and spleen. Decreased trend of palmitic acid substitution in some of GSLs fractions points at possible role of palmitoylation in the signal transduction pathway of TNFR1.

neutral glycosphingolipids; HPTLC immunostaining; gene knockout mice; TNFreceptor 1; brain; spleen

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