Cell surface sphingolipid glycohydrolases in neuronal differentiation and aging in culture

Abstract

J. Neurochem. (2011) 116, 891–899. Abstract Qualitative and quantitative changes in glycosphingolipids, together with changes in the expression of the corresponding glycosyltransferases, have been reported along neuronal differentiation and aging. Plasma membrane (PM) glycosphingolipid pattern and content are the result of a complex network of metabolic pathways, including those potentially involving the activity of PM glycohydrolases. We analyzed the total cell activities of sialyltransferase I, II and IV, sialidase, β‐galactosidase and β‐glucosidase, and the PM‐associated activities of sialidase Neu3, β‐galactosidase, Conduritol B Epoxide‐sensitive β‐glucosidase and β‐glucosidase GBA2 in rat cerebellar granule cells along differentiation and aging in culture. Sialyltransferase activities increased during cell differentiation, in agreement with the known increase of the total ganglioside content during neuronal maturation. The remodeling of ganglioside pattern could be because of the augmented activities of total sialidase and, within PM, to the action of the cell surface associated sialidase Neu3. Sialidase activities remained high during aging, in agreement with the known progressive ganglioside reduction in brain senescence. As PM β‐galactosidase and β‐glucosidase activities and parallely ceramide levels markedly increased along in vitro aging, PM ceramide production in neurons might be because of local catabolism of glycosphingolipids and not only to that of sphingomyelin, as already reported in human fibroblasts.

Reduced Susceptibility to Colitis-Associated Colon Carcinogenesis in Mice Lacking Plasma Membrane-Associated Sialidase

“…We and others have shown that NEU3 can modulate biological processes, including neuronal differentiation [9]–[11], T-cell activation [12], monocyte differentiation [13], cell adhesion and motility [14], [15], and the onset of a diabetic phenotype [16]. In addition, we demonstrated that human NEU3 is upregulated in terms of both enzymatic activity and mRNA level in many human cancers, including colon [17], renal [18], prostate [19], and ovarian [20] cancers.…”

Segmental Aging Underlies the Development of a Parkinson Phenotype in the AS/AGU Rat

“…Interestingly, p16 Ink4a and SA-β-Gal expression can be driven by β-amyloid in senescent astrocytes; however, the accumulation of SA-β-gal depends on pRB (retinoblastoma) functionality and is associated with the p21 WAF1 -mediated senescence pathway, independently of SA-β-gal status [38,39]. Others have stipulated that an overall increase in SA-β-gal expression in the aging brain may be associated with changes in ganglioside abundance, but ultimately this can also be linked to senescent neurons and can be considered as a useful surrogate marker of neurodegenerative diseases [40,41,42]. Similarly, up-regulation of p16 Ink4a is a consistent feature of cellular senescence and age-related morbidity in a range of in vitro and in vivo models.…”

A lysosome‐plasma membrane‐sphingolipid axis linking lysosomal storage to cell growth arrest

“…Within the PM, SLs are not only structural components but also participate, through their interaction with PM-associated proteins, in controlling several signal transduction pathways that are fundamental to maintaining cell homeostasis (13). Interestingly, the in situ modification of the PM SL composition represents a stimulus able to affect several signaling pathways, including those that control cell death and growth arrest (14)(15)(16)(17)(18). Based on these observations, in this work we investigate the involvement of PM glycosphingolipid catabolic pathways in the mechanisms linking lysosomal impairment to the onset of cell damage.…”