Sandro Sonnino - Academia.edu (original) (raw)

Papers by Sandro Sonnino

Journal of Biological Chemistry, 2011

Journal of Neurochemistry, 2019

† Dedicated to the memory of Dr. Riccardo Casellato, whose scientific contribution was fundamenta... more † Dedicated to the memory of Dr. Riccardo Casellato, whose scientific contribution was fundamental to improve the synthesis of photoactivable gangliosides.

Glycoconjugate Journal, 2000

The conformations and dynamics of gangliosides GM1, GM2, 6'-GM2 and GM4 have been studied by ... more The conformations and dynamics of gangliosides GM1, GM2, 6'-GM2 and GM4 have been studied by computational means, and the results compared to NMR data. Unconstrained conformational searches were run using the AMBER* force field augmented by MNDO derived parameters for the Neu5Ac anomeric torsion, the GB/SA water solvation model, and the MC/EM alogorithm; extended (10–12[emsp4 ]ns) dynamic simulations in GB/SA

Neurochemistry International, 1992

A~tract-The incubation of cultured rat cerebellar granule cells w,th a photoreactwe denvatwe of r... more A~tract-The incubation of cultured rat cerebellar granule cells w,th a photoreactwe denvatwe of radiolabeled GMI ganghoside, [3H]GMI(N3), followed by dlummation, led to the speofic assoclahon of ganghoslde to cell proteins After 30 rain of incubaUon only a few out of the cell proteins became radlolabeled Two of these, at apparent molecular weights of 95 and 112 kDa, are interacting with the portion of associated ganghoslde that is released by trypsin treatment, others, in the region between 31 and 44 kDa, are probably bound to molecules of ganghoside inserted into the outer membrane layer, thus showing that the ganghos~de association to the cell surface is a selective phenomenon, mvolving specific proteins Increasing the incubation time up to 24 h resulted in a larger number of ra&olabeled proteins, probably as a consequence of the internahzatlon and metabolic processing of admimstered [3H]GM I(N3) In fact, photoreactive and ra&oactwe metabolic denvat,ves of [~H]GMI(N0 can also interact with a number of proteins After 24 h incubation, some radioactivity was also associated to cytosohc proteins Again in this case the interaction with proteins seems to be a specific process lnvolwng only a few out of the total cytosohc proteins Ganghos~des, smhc acid containing glycosphmgollplds, are components of the external hpld layer of vertebrate cells plasma membrane and are *Parts of the results of this refereed paper were presented at the ESN workshop on Glycoconjugate~ and Neuronal Membrane Functton, held in Leipzig, 23

Neurochemistry International, 1982

Abstraet-A procedure for accurate densitometric quantification of gangliosides separated by two-d... more Abstraet-A procedure for accurate densitometric quantification of gangliosides separated by two-dimensional thin layer chromatograph 3 is reported. The procedure was set up employing 9 different pure gangliosides and was applied to the analysis of calf and pig brain gangliosides. Silica gel high performance thin layer plates, 10 × 10cm. were two-dimensionally developed at 18-20 C with the following solvents: chloroform/methanol;0.2°~, aqueous CaCI.,. 50/4010 by volume, for the first run: n-propanol 17M NHaOH,water. 6,'2;1 by volume for the second run. Ganglioside spots were visualized b3 spraying with an Ehrlich reagent, which is specific for sialic acid. and heating at 120 C for 15rain. The spots were quantified by sequential scanning densitometry, linear responses being obtained for ganglioside amounts on the plate ranging from 0.1 to 6 nmol as bound siatic acid. The reproducibilit 3 of densitometric responses resulted to be acceptable since the standard deviation values were lower than ± 15". of the mean values also for those ganglioside species contained in minor proportions. The ganglioside mixtures of calf and pig brain were resolved in about 20 spots. Of these 9 corresponded to gangliosides GM3. GM2. GMI. Fuc-GMI. GDIa, GDlb. Fuc-GDlb. GTIb and GQlb. which were identified with certainty and quantified. The identification of GM3 (carrying N-glycolylneuraminic acidl. GD3. GDla Icarrying N-acetyl-and N-glycolyl-neuraminic acid) and GTIa was only tentative. All the other spots corresponded to unidentified gangliosides, some of them possibly new species.

Journal of Neurochemistry, 1991

The Journal of Lipid Research, 2010

and ovarian cancers, neuroblastoma, lymphoma, and leukemia. Many pieces of evidence indicate a li... more and ovarian cancers, neuroblastoma, lymphoma, and leukemia. Many pieces of evidence indicate a link between HPR's antitumor effect and the metabolism of sphingolipids in tumor cells. As for many other anticancer drugs, the studies in tumor cell lines indicated that apoptosis is the major cytotoxic mechanism for HPR [even if the toxic effect of HPR is likely very complex and at least in part due to nonapoptotic mechanisms (2, 3)], and HPR-induced apoptosis in cancer cells has been ascribed to the increased cellular levels of ceramide, a sphingolipid mediator playing multiple roles in apoptotic signaling, elicited by HPR (4). The main metabolic mechanism responsible for HPR-induced production of ceramide is represented by de novo synthesis. Exposure to HPR of human neuroblastoma (5) and prostate cancer cells (6) resulted in a time-and dose-dependent increase in the activity of serine palmitoyltansferase and (dihydro)ceramide synthase, which catalyze early steps in the biosynthesis of ceramide and derived sphingolipids (7), and the treatment of cultured cells with pharmacological inhibitors of these enzymes was able to block HPR-induced ceramide increase (5, 6, 8). However, the effects of HPR on sphingolipid metabolism are probably much more complex and still poorly understood. For example, the possible role of sphingomyelin turnover due to the action of sphingomyelinases in the HPRelicited ceramide production is still controversial, and confl icting results have been reported (8, 9). In neuroblastoma Abstract The dihydroceramide, ceramide, sphingomyelin, lactosylceramide, and ganglioside species of A2780 human ovarian carcinoma cells treated with the synthetic retinoids N-(4-hydroxyphenyl)retinamide (fenretinide, 4-HPR) and 4-oxo-N-(4-hydroxyphenyl)retinamide (4-oxo-4-HPR) in culture were characterized by ESI-MS. We characterized 32 species of ceramide and dihydroceramide, 15 of sphingomyelin, 12 of lactosylceramide, 9 of ganglioside GM2, and 6 of ganglioside GM3 differing for the long-chain base and fatty acid structures. Our results indicated that treatment with both 4-HPR and 4-oxo-4-HPR led to a marked increase in dihydroceramide species, while only 4-oxo-4-HPR led to a minor increase of ceramide species. Dihydroceramides generated in A2780 cells in response to 4-HPR or 4-oxo-4-HPR differed for their fatty acid content, suggesting that the two drugs differentially affect the early steps of sphingolipid synthesis. Dihydroceramides produced upon treatments with the drugs were further used for the synthesis of complex dihydrosphingolipids, whose levels dramatically increased in drug-treated cells.

The Journal of Lipid Research, 2003

Treatment with methyl-␤-cyclodextrin (MCD) induced a time-and dose-dependent efflux of cholestero... more Treatment with methyl-␤-cyclodextrin (MCD) induced a time-and dose-dependent efflux of cholesterol, sphingolipids, and phosphatidylcholine (PC) from cerebellar neurons differentiated in culture. With a "mild" treatment, the loss of cell lipids induced a deep reorganization of the remaining membrane lipids. In fact, the amount of PC associated with a Triton X-100-insoluble membrane fraction (highly enriched in sphingolipids and cholesterol in nontreated cells) was lowered by the treatment. This suggested a reduction of the lipid domain area. However, the cholesterol and sphingolipid enrichment of this fraction remained substantially unchanged, suggesting the existence of dynamic processes aimed at preserving the segregation of cholesterol and sphingolipids in membrane domains. Under these conditions, the lipid membrane domains retained the ability to sort signaling proteins, such as Lyn and c-Src, but cells displayed deep alterations in their membrane permeability. However, normal membrane permeability was restored by loading cells with cholesterol. When MCD treatment was more stringent, a large loss of cell lipids occurred, and the lipid domains were much less enriched in cholesterol and lost the ability to sort specific proteins. The loss of the integrity and properties of lipid domains was accompanied by severe changes in the membrane permeability, distress, and eventually cell death.-Ottico, E., A.

Journal of Biological Chemistry, 2002

FEBS Letters, 2009

Caveolin-1, and probably also-2 and-3, can organize multimolecular membrane complexes involved in... more Caveolin-1, and probably also-2 and-3, can organize multimolecular membrane complexes involved in transmembrane traffic, cell adhesion and signal transduction. In this review, we discuss on the importance of caveolin membrane environment in regulating the architecture and function of such complexes, with a special emphasis on the role of sphingolipids.

Chemistry and Physics of Lipids, 1988

N-Glycolylneuraminic acid containing GM 1, GM l(NeuGc), was prepared by semisynthetic procedure. ... more N-Glycolylneuraminic acid containing GM 1, GM l(NeuGc), was prepared by semisynthetic procedure. The procedure makes use of GM 1 ganglioside deacetylated at the level of sialic acid residue (deAc-GM 1) and of 1,3-dioxalan-2,4-dione. DeAc-GM 1 is prepared from GM 1 by alkaline hydrolysis in the presence of tetramethylammonium hydroxide and the glycolylating compound by reaction of glycolic acid with phosgene in dioxane, followed by cyclization under vacuum. Mass spectrometric and nuclear magnetic resonance spectroscopy analyses clearly indicated the presence, in the neosynthesized ganglioside of a glycolic group in the sialic acid residue. Laser-light scattering measurements show that GM l(NeuGc) aggregates in aqueous media being present in solution as micelles with a molecular weight of 576,000 and a hydrodynamic radius of 62.4/~, as determined at 25°C. GM 1 (NeuGc) promotes neurite outgrowth in N-2a cells to a similar degree as GMI(NeuAc), but shows different behaviour under treatment with sialidase from Arthrobacter ureafaciens.