P-244 - Non-enzymatic oxidation of ganglioside studied by mass spectrometry: Gm1 as a case study

Abstract

Gangliosides are acidic glycosphingolipids (GLS) found in cells membrane, lipid raft domains, and are particularly abundant in central nervous systems, where they play important roles. Alteration in gangliosides has been correlated with the development of diseases, such as neurodegenerative diseases, and inflammation, usually associated with oxidative stress. However, knowledge regarding oxidation of gangliosides is scarce. In this study we evaluated the effect of radical oxidation in GM1 (Neu5Acα2–3 (Galβ1–3GalNAcβ1–4) Galβ1–4Glcβ1Cer) under Fenton reaction conditions, using ESI-MS and MS/MS. Oxidation of GM1 yield a plethora of product including oxygenated GM1 and several GLS formed due to oxidative decomposition of the glycosidic moiety, leading to the formation of other gangliosides:GM2, GM3, asialo-GM1, asialo-GM; small GSL as LacCer, GalCer and ceramides. Non-enzymatic oxidation of GM1 under oxidative stress contributes to the generation of other gangliosides that may participate in the imbalance of gangliosides metabolism in vivo, through uncontrolled enzymatic pathways and, consequently, play some role in neurodegenerative processes.