Activity of plasma membrane β‐galactosidase and β‐glucosidase

Aureli, Massimo; Masilamani, Anie P.; Illuzzi, Giuditta; Loberto, Nicoletta; Scandroglio, Federica; Prinetti, Alessandro; Chigorno, Vanna; Sonnino, Sandro

doi:10.1016/j.febslet.2009.06.048

Cited by 53 publications

(51 citation statements)

References 12 publications

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“…1, besides the action of the multiple SMases isoforms, ceramide can also be generated through the hydrolysis of glycosphingolipids operated by a set of specific glycohydrolases, mainly located in the endo- lysosomal compartment, but also detectable at the external site of the cell surface, as demonstrated by relatively recent studies from our and other groups [52,53]. This finding supports the functional relevance of GSL breakdown as additional mechanism of ceramide production of potential impact in cancer therapies, including radiation.…”

Section: Glycohydrolases Activation In Response To Ionizing Radiationsupporting

confidence: 83%

“…The enzyme is sensitive to Conduritol B Epoxide (CBE) inhibition. While GBA1 enzyme has always been described as a lysosomalassociated enzyme, some recent studies described for the first time the presence of a CBE-sensitive β-glucosidase activity also at the cell surface [52,72].…”

Section: Glycohydrolases Activation In Response To Ionizing Radiationmentioning

confidence: 99%

“…Besides the lysosomal enzymes, the β-galactosidase activity has also been detected at the plasma membrane level in several cell lines [52], although the identity of the protein/proteins responsible for the β-galactosidase activity is still unknown. At least three different β-glucosidases (β-Glc) have been described: a lysosomal β-glucocerebrosidase (GBA; EC 3.2.1.45) [68], a non-lysosomal β-glucosylceramidase (GBA2; EC 3.2.1.45) [69] and a cytosolic β-glucosidase (GBA3; EC 3.2.1.21) [70].…”

Section: Glycohydrolases Activation In Response To Ionizing Radiationmentioning

confidence: 99%

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Exploring the link between ceramide and ionizing radiation

et al. 2014

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The aim of radiotherapy is to eradicate cancer cells with ionizing radiation; tumor cell death following irradiation can be induced by several signaling pathways, most of which are triggered as a consequence of DNA damage, the primary and major relevant cell response to radiation. Several lines of evidence demonstrated that ceramide, a crucial sensor and/or effector of different signalling pathways promoting cell cycle arrest, death and differentiation, is directly involved in the molecular mechanisms underlying cellular response to irradiation. Most of the studies strongly support a direct relationship between ceramide accumulation and radiation-induced cell death, mainly apoptosis; for this reason, defining the contribution of the multiple metabolic pathways leading to ceramide formation and the causes of its dysregulated metabolism represent the main goal in order to elucidate the ceramide-mediated signaling in radiotherapy. In this review, we summarize the current knowledge concerning the different routes leading to ceramide accumulation in radiation-induced cell response with particular regard to the role of the enzymes involved in both ceramide neogenesis and catabolism. Emphasis is placed on sphingolipid breakdown as mechanism of ceramide generation activated following cell irradiation; the functional relevance of this pathway, and the role of glycosphingolipid glycohydrolases as direct targets of ionizing radiation are also discussed. These new findings add a further attractive point of investigation to better define the complex interplay between sphingolipid metabolism and radiation therapy.

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Section: Glycohydrolases Activation In Response To Ionizing Radiationsupporting

confidence: 83%

Section: Glycohydrolases Activation In Response To Ionizing Radiationmentioning

confidence: 99%

Section: Glycohydrolases Activation In Response To Ionizing Radiationmentioning

confidence: 99%

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Exploring the link between ceramide and ionizing radiation

et al. 2014

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“…These findings raise the possibility of a novel paradigm that not only the specific identity of a bioactive sphingolipid is important, but the enzyme from which it is produced within a subcellular location may dictate its biologic function. Based on our studies, the subcellular topology was not defined, but we speculate that ASM and GBA1 are acting on their respective substrates at somewhat distinct points in the endolysosomal system, which is involved in recycling SM and glucosylceramide from the plasma membrane to the lysosome (30,31). In terms of transducing a signal, the plasma membrane or early endosomes appear to be a more likely candidate than the lysosome, which itself is encased by the limiting membrane, where ASM and GBA1 are in the lumen, bound to and degrading internal membranes within the lysosome.…”

Section: Regulation Of Il-6 By Pkc and Sphingolipid Metabolism-mentioning

confidence: 99%

Defining a Role for Acid Sphingomyelinase in the p38/Interleukin-6 Pathway

Perry

Newcomb²,

Adada³

et al. 2014

Journal of Biological Chemistry

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Background: Sphingolipids are important in multiple biological processes, but there is a lack of understanding of the pathways that mediate these effects. Results: Acid sphingomyelinase is involved in p38 activation, interleukin-6 production, and cancer cell invasion. Conclusion: Acid sphingomyelinase plays a role in inflammatory, proinvasive signaling in cancer cells. Significance: This work expands the understanding of acid sphingomyelinase signaling and downstream biology.

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“…However, an additional level of regulation of glycosphingolipid expression has been recently suggested to occur at the plasma membrane level, with the existence being reported of a plasma membrane-associated sialidase, termed Neu3, which is able to trigger selective ganglioside desialylation in different cell types (17)(18)(19). Moreover, ␤-hexosaminidase (20), ␤-glucosidase, and ␤-galactosidase (21) activities have also been demonstrated at the cell surface, suggesting their role in the remodeling of the plasma membrane glycosphingolipids, thus contributing to modulate lipid composition and membrane organization, and consequently, different signaling processes (21,22).…”

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confidence: 99%

Neobiosynthesis of Glycosphingolipids by Plasma Membrane-associated Glycosyltransferases*

Crespo¹,

Demichelis²,

Daniotti

2010

Journal of Biological Chemistry

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Gangliosides, complex glycosphingolipids containing sialic acids, are synthesized in the endoplasmic reticulum and in the Golgi complex. These neobiosynthesized gangliosides move via vesicular transport to the plasma membrane, becoming components of the external leaflet. Gangliosides can undergo endocytosis followed by recycling to the cell surface or sorting to the Golgi complex or lysosomes for remodeling and catabolism. Recently, glycosphingolipid catabolic enzymes (glycohydrolases) have been found to be associated with the plasma membrane, where they display activity on the membrane components. In this work, we demonstrated that ecto-ganglioside glycosyltransferases may catalyze ganglioside synthesis outside the Golgi compartment, particularly at the cell surface. Specifically, we report the first direct evidence of expression and activity of CMP-NeuAc: GM3 sialyltransferase (Sial-T2) at the cell surface of epithelial and melanoma cells, with membrane-integrated ectoSial-T2 being able to sialylate endogenously synthesized GM3 ganglioside as well as exogenously incorporated substrate. Interestingly, we also showed that ecto-Sial-T2 was able to synthesize GD3 ganglioside at the cell surface using the endogenously synthesized cytidine monophospho-N-acetylneuraminic acid (CMP-NeuAc) available at the extracellular milieu. In addition, the expression of UDP-GalNAc:LacCer/GM3/ GD3 N-acetylgalactosaminyltransferase (GalNAc-T) was also detected at the cell surface of epithelial cells, whose catalytic activity was only observed after feeding the cells with exogenous GM3 substrate. Thus, the relative interplay between the plasma membrane-associated glycosyltransferase and glycohydrolase activities, even when acting on a common substrate, emerges as a potential level of regulation of the local glycosphingolipid composition in response to different external and internal stimuli.

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Activity of plasma membrane β‐galactosidase and β‐glucosidase

Cited by 53 publications

References 12 publications

Exploring the link between ceramide and ionizing radiation

Exploring the link between ceramide and ionizing radiation

Defining a Role for Acid Sphingomyelinase in the p38/Interleukin-6 Pathway

Neobiosynthesis of Glycosphingolipids by Plasma Membrane-associated Glycosyltransferases*

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