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Production of multiple brain-like ganglioside species is dispensable for fas-induced apoptosis of lymphoid cells.

Popa I, Therville N, Carpentier S, Levade T, Cuvillier O, Portoukalian J - PLoS ONE (2011)

Bottom Line: Activation of an acid sphingomyelinase (aSMase) leading to a biosynthesis of GD3 disialoganglioside has been associated with Fas-induced apoptosis of lymphoid cells.Hampering ganglioside production by inhibiting the key enzyme glucosylceramide synthase did not abrogate the apoptotic process.In addition, GM3 synthase-deficient lymphoid cells underwent Fas-induced apoptosis, suggesting that gangliosides are unlikely to play an indispensable role in transducing Fas-induced apoptosis of lymphoid cells.

View Article: PubMed Central - PubMed

Affiliation: Laboratoire de Recherche Dermatologique, EA4169 Université de Lyon-1, Hôpital Edouard Herriot, Lyon, France.

ABSTRACT
Activation of an acid sphingomyelinase (aSMase) leading to a biosynthesis of GD3 disialoganglioside has been associated with Fas-induced apoptosis of lymphoid cells. The present study was undertaken to clarify the role of this enzyme in the generation of gangliosides during apoptosis triggered by Fas ligation. The issue was addressed by using aSMase-deficient and aSMase-corrected cell lines derived from Niemann-Pick disease (NPD) patients. Fas cross-linking elicited a rapid production of large amounts of complex a- and b-series species of gangliosides with a pattern and a chromatographic behavior as single bands reminiscent of brain gangliosides. The gangliosides were synthesized within the first ten minutes and completely disappeared within thirty minutes after stimulation. Noteworthy is the observation that GD3 was not the only ganglioside produced. The production of gangliosides and the onset of apoptotic hallmarks occurred similarly in both aSMase-deficient and aSMase-corrected NPD lymphoid cells, indicating that aSMase activation is not accountable for ganglioside generation. Hampering ganglioside production by inhibiting the key enzyme glucosylceramide synthase did not abrogate the apoptotic process. In addition, GM3 synthase-deficient lymphoid cells underwent Fas-induced apoptosis, suggesting that gangliosides are unlikely to play an indispensable role in transducing Fas-induced apoptosis of lymphoid cells.

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Related in: MedlinePlus

Schematic view of ganglioside biosynthesis in mammalian cells.Sequential addition of sialic acid residues to lactosylceramide (LacCer) by the specific sialyl-transferases I, II and III produces the monosialo, disialo and trisialo-gangliosides GM3, GD3 and GT3, respectively. These glycolipids serve as precursors for the a, b and c series of gangliosides, which are formed by stepwise glycosylation, i.e., by addition of N-acetyl-beta-galactosamine (GalNAc), beta-galactose (Gal) and sialic acid by a GalNAc-transferase, a galactosyl-transferase and a sialyl-transferase, respectively.
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pone-0019974-g007: Schematic view of ganglioside biosynthesis in mammalian cells.Sequential addition of sialic acid residues to lactosylceramide (LacCer) by the specific sialyl-transferases I, II and III produces the monosialo, disialo and trisialo-gangliosides GM3, GD3 and GT3, respectively. These glycolipids serve as precursors for the a, b and c series of gangliosides, which are formed by stepwise glycosylation, i.e., by addition of N-acetyl-beta-galactosamine (GalNAc), beta-galactose (Gal) and sialic acid by a GalNAc-transferase, a galactosyl-transferase and a sialyl-transferase, respectively.

Mentions: Of importance is the observation that GD3 was not the only ganglioside produced upon Fas ligation. Conversely, we found within a few minutes an accumulation of b-series (e.g., GD1b and GT1b) as well as a-series (e.g., GM1a and GD1a) gangliosides (see Figure 7 and the accompanying legend for the biosynthetic pathways of gangliosides), demonstrating that GalNAc-transferase and other transferases are present, but normally inactive in these cells. It should be pointed out that the relevant hydrolases also should be present in cells but in the inactive form since all de novo synthesized gangliosides totally disappeared in less than one hour. No traces of gangliosides was found in the buffer, thus ruling out any shedding to explain this rapid disappearance.


Production of multiple brain-like ganglioside species is dispensable for fas-induced apoptosis of lymphoid cells.

Popa I, Therville N, Carpentier S, Levade T, Cuvillier O, Portoukalian J - PLoS ONE (2011)

Schematic view of ganglioside biosynthesis in mammalian cells.Sequential addition of sialic acid residues to lactosylceramide (LacCer) by the specific sialyl-transferases I, II and III produces the monosialo, disialo and trisialo-gangliosides GM3, GD3 and GT3, respectively. These glycolipids serve as precursors for the a, b and c series of gangliosides, which are formed by stepwise glycosylation, i.e., by addition of N-acetyl-beta-galactosamine (GalNAc), beta-galactose (Gal) and sialic acid by a GalNAc-transferase, a galactosyl-transferase and a sialyl-transferase, respectively.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3101221&req=5

pone-0019974-g007: Schematic view of ganglioside biosynthesis in mammalian cells.Sequential addition of sialic acid residues to lactosylceramide (LacCer) by the specific sialyl-transferases I, II and III produces the monosialo, disialo and trisialo-gangliosides GM3, GD3 and GT3, respectively. These glycolipids serve as precursors for the a, b and c series of gangliosides, which are formed by stepwise glycosylation, i.e., by addition of N-acetyl-beta-galactosamine (GalNAc), beta-galactose (Gal) and sialic acid by a GalNAc-transferase, a galactosyl-transferase and a sialyl-transferase, respectively.
Mentions: Of importance is the observation that GD3 was not the only ganglioside produced upon Fas ligation. Conversely, we found within a few minutes an accumulation of b-series (e.g., GD1b and GT1b) as well as a-series (e.g., GM1a and GD1a) gangliosides (see Figure 7 and the accompanying legend for the biosynthetic pathways of gangliosides), demonstrating that GalNAc-transferase and other transferases are present, but normally inactive in these cells. It should be pointed out that the relevant hydrolases also should be present in cells but in the inactive form since all de novo synthesized gangliosides totally disappeared in less than one hour. No traces of gangliosides was found in the buffer, thus ruling out any shedding to explain this rapid disappearance.

Bottom Line: Activation of an acid sphingomyelinase (aSMase) leading to a biosynthesis of GD3 disialoganglioside has been associated with Fas-induced apoptosis of lymphoid cells.Hampering ganglioside production by inhibiting the key enzyme glucosylceramide synthase did not abrogate the apoptotic process.In addition, GM3 synthase-deficient lymphoid cells underwent Fas-induced apoptosis, suggesting that gangliosides are unlikely to play an indispensable role in transducing Fas-induced apoptosis of lymphoid cells.

View Article: PubMed Central - PubMed

Affiliation: Laboratoire de Recherche Dermatologique, EA4169 Université de Lyon-1, Hôpital Edouard Herriot, Lyon, France.

ABSTRACT
Activation of an acid sphingomyelinase (aSMase) leading to a biosynthesis of GD3 disialoganglioside has been associated with Fas-induced apoptosis of lymphoid cells. The present study was undertaken to clarify the role of this enzyme in the generation of gangliosides during apoptosis triggered by Fas ligation. The issue was addressed by using aSMase-deficient and aSMase-corrected cell lines derived from Niemann-Pick disease (NPD) patients. Fas cross-linking elicited a rapid production of large amounts of complex a- and b-series species of gangliosides with a pattern and a chromatographic behavior as single bands reminiscent of brain gangliosides. The gangliosides were synthesized within the first ten minutes and completely disappeared within thirty minutes after stimulation. Noteworthy is the observation that GD3 was not the only ganglioside produced. The production of gangliosides and the onset of apoptotic hallmarks occurred similarly in both aSMase-deficient and aSMase-corrected NPD lymphoid cells, indicating that aSMase activation is not accountable for ganglioside generation. Hampering ganglioside production by inhibiting the key enzyme glucosylceramide synthase did not abrogate the apoptotic process. In addition, GM3 synthase-deficient lymphoid cells underwent Fas-induced apoptosis, suggesting that gangliosides are unlikely to play an indispensable role in transducing Fas-induced apoptosis of lymphoid cells.

Show MeSH
Related in: MedlinePlus