Structural characterization of the disialogangliosides of murine peritoneal macrophages.

Autor: Yohe, Herbert C., Ye, Song, Reinhold, Bruce B., Reinhold, Vernon N.
Zdroj: Glycobiology; Dec1997, Vol. 7 Issue 12, p1215-1227, 13p
Abstrakt: Sialoglycosphingolipids (gangliosides) have been increasingly implicated as regulators of membrane signaling events. Macrophage ganglioside patterns dramatically increase in complexity when murine peritoneal macrophages are stimulated with the appearance of the sialidase-sensitive monosialoganglioside GMlb (cisGMl) as a major component Gangliosides from stimulated murine peritoneal macrophages were separated into monosialo and polysialo fractions and the polysialo fraction structurally characterized by enzymatic, chemical, and mass spectra methods. All detectable components of the polysialo fraction were determined to be disialogangliosides. Treatment of the polysialo fraction with siali-dase produced mostly the sialidase-resistant monosialoganglioside, GMIa, and a minor amount of asiaJoGMI. Perio-date oxidation and mass spectrometry analyses demonstrated the lack of tandem disialo moieties which indicated the absence of GD1b or GD1c (GDI) entities. The combined data showed the major disialogangliosides consisted of GDla entities comprising IV3-NeuAc,II3NeuAc-GgOse4Cer, IV3-NeuGc,II3NeuAc-GgOse4Cer, IV3NeuAc,II3NeuGc-GgOse4Cer, and IV3-NeuGc,II3NeuGc-GgOse4Cer. Minor components consisted of GDlα entities, IV3NeuAc, III6NeuAcGgOse4Cer, IV3NeuGc, III6NeuGcGgOse4Cer, and also positional iso-mer(s) of GDlα(NeuAc, NeuGc). These isomeric components were identified by collision analysis and tandem mass spectrometry. Consistent with previous analyses, the cer-amide portion of all polysialo (disialo) gangliosides contained solely C18 sphingosine with C16 and C24 fatty acid moieties. These results, combined with the previous characterization of macrophage monosialogangliosides, indicate normal murine macrophage ganglioside biosynthesis proceeds along the “a” ganglioside pathway, e.g., GM3→GM2→GMla→GDlα, and the proposed asialogan-glioside or “α” pathway, asialoGMl→GMlb→GDlα. The presence of totally sialidase-sensitive gangliosides appears to be characteristic of functional murine peritoneal macrophages while they are reduced in genetically impaired cells. [ABSTRACT FROM PUBLISHER]
Databáze: Complementary Index