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Orie Tajima

Publications and source records attributed to Orie Tajima.

4 recordsLinked to original sources

Targeted disruption of Gb3/CD77 synthase gene resulted in the complete deletion of globo-series glycosphingolipids and loss of sensitivity to verotoxins.

To examine whether globotriaosylceramide (Gb3/CD77) is a receptor for verotoxins (VTs) in vivo, sensitivity of Gb3/CD77 synthase null mutant mice to VT-2 and VT-1 was analyzed. Although wild-type mice died after administration of 0.02 microg of VT-2 or 1.0 microg of VT-1, the mutant mice showed no reaction to doses as much as 100 times that administered to wild types. Expression analysis of Gb3/CD77 in mouse tissues with antibody revealed that low, but definite, levels of Gb3/CD77 were expressed in the microvascular endothelial cells of the brain cortex and pia mater and in renal tubular capillaries. Corresponding to the Gb3/CD77 expression, tissue damage with edema, congestion, and cytopathic changes was observed, indicating that Gb3/CD77 (and its derivatives) exclusively function as a receptor for VTs in vivo. The lethal kinetics were similar regardless of lipopolysaccharide elimination in VT preparation, suggesting that basal Gb3/CD77 levels are sufficient for lethal effects of VTs.

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Over-expression of GM1 enhances cell proliferation with epidermal growth factor without affecting the receptor localization in the microdomain in PC12 cells.

Sialic acid-containing glycosphingolipids, gangliosides, are expressed at high levels in the nerve tissues and various tumor cells. Although a number of studies on the roles of gangliosides in the regulation of cell proliferation have been performed, the mechanisms for the regulation are not well understood. We established PC12 transfectant cells over-expressing GM1 using cloned beta1,3-galactosyltransferase (EC: 2.4.1.62) cDNA, and analyzed their growth and growth signals with epidermal growth factor (EGF). Over-expression of GM1 enhanced the cell proliferation with EGF under low serum culture conditions. The phosphorylation levels of EGF receptor and downstream MAP kinases after EGF stimulation were sustained even after 60 min in the transfectant cells. In contrast with Swiss3T3 cells, in which we previously reported growth suppression with GM1 over-expression due to a dramatic change in the intracellular localization of PDGF receptor, PC12 transfectant cells with beta1,3-galactosyltransferase cDNA showed no clear changes in the intracellular localization of EGF receptor in the microdomain/raft fractionation experiments compared with the vector control cells. These results suggested that the effects of GM1 expression on the nature of microdomains and growth signals depend on the cell types and receptors analyzed.

Animals↗

Glycosphingolipids in engineered mice: insights into function.

Recent success in the cloning of glycosyl-transferase genes involved in the synthesis of GSLs has enabled us to modulate the expression profiles of GSLs in cultured cells and experimental animals, and allowed novel approaches to obtain clear elucidation of individual enzyme products by observing the resulting phenotypic changes in the mutant animals and transfected cells. In this review, recent progress in the study of glycosyltransferases involved in the synthesis and modification of GSLs has been summarized with special emphasis on their function.

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