Structural characterization and dynamics of globotetraosylceramide in vascular endothelial cells under TNF-α stimulation |
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Authors: | Tetsuya Okuda Sin-ichi Nakakita Ken-ichi Nakayama |
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Institution: | (1) Glycolipids Function Analysis Team, Health Technology Research Center, National Institute of Advanced Industrial Science and Technology (AIST), 2217-14 Hayashi, Takamatsu, Kagawa 761-0395, Japan;(2) Department of Functional Glycomics, Life Science Research Center, Kagawa University, Kagawa, Japan |
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Abstract: | In several vascular inflammatory reactions (i.e. immunity and thrombosis) inflammatory mediators lead to the activation of vascular endothelial cells (EC). To date, a number
of functional molecules induced on the surface of activated-EC have been identified. We report here that Globotetraosylceramide
(Gb4), a glycosphingolipid expressed in EC, is a novel inducible molecule on EC activated by TNF-α. The cell surface expression
of Gb4 is increased in a time-dependent manner under TNF-α stimulation, which shows distinct expression kinetics of major
proteins induced by TNF-α on EC. MALDI-TOF-MS analysis revealed that the enhanced Gb4 predominantly contains C24:0 fatty acid
in the ceramide moiety. Isolated caveolae/lipid raft-enriched detergent insoluble membrane domains in activated-EC predominantly
contain this molecular species of Gb4. Gb4 containing C16:0 fatty acid in the ceramide moiety, which is known to constitute
the major species of Gb4 in plasma, is also found as a major molecular species in EC. These observations indicate that Gb4,
especially with very long fatty acid, is enhanced in EC during its inflammatory reaction, and suggest the potential utility
of Gb4 as a biomarker for monitoring inflammation status of EC involving its related diseases. |
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