Production of Multiple Brain-Like Ganglioside Species Is Dispensable for Fas-Induced Apoptosis of Lymphoid Cells

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

A Deficiency of Ceramide Biosynthesis Causes Cerebellar Purkinje Cell Neurodegeneration and Lipofuscin Accumulation

Sphingolipids, lipids with a common sphingoid base (also termed long chain base) backbone, play essential cellular structural and signaling functions. Alterations of sphingolipid levels have been implicated in many diseases, including neurodegenerative disorders. However, it remains largely unclear whether sphingolipid changes in these diseases are pathological events or homeostatic responses. Furthermore, how changes in sphingolipid homeostasis shape the progression of aging and neurodegeneration remains to be clarified. We identified two mouse strains, flincher (fln) and toppler (to), with spontaneous recessive mutations that cause cerebellar ataxia and Purkinje cell degeneration. Positional cloning demonstrated that these mutations reside in the Lass1 gene. Lass1 encodes (dihydro)ceramide synthase 1 (CerS1), which is highly expressed in neurons. Both fln and to mutations caused complete loss of CerS1 catalytic activity, which resulted in a reduction in sphingolipid biosynthesis in the brain and dramatic changes in steady-state levels of sphingolipids and sphingoid bases. In addition to Purkinje cell death, deficiency of CerS1 function also induced accumulation of lipofuscin with ubiquitylated proteins in many brain regions. Our results demonstrate clearly that ceramide biosynthesis deficiency can cause neurodegeneration and suggest a novel mechanism of lipofuscin formation, a common phenomenon that occurs during normal aging and in some neurodegenerative diseases

Caractéristiques spectrales et énergétiques du rayonnement émis par un laser en Y à deux milieux amplificateurs YAG:Nd3+^{3+}

Nous présentons l'étude expérimentale des caractéristiques spectrales et énergétiques du rayonnement émis par un laser en Y possédant deux milieux amplificateurs YAG :Nd$^{3+}$. Nous réalisons une combinaison des champs issus des deux milieux actifs par division d'amplitude sur une séparatrice intracavité. Nous montrons que le spectre des fréquences temporelles s'auto-adapte pour permettre la sommation cohérente des deux champs

Combinaison cohérente extra-cavité de diodes lasers monomodes fibrées dans un dispositif interférométrique tout-fibré

Nous rapportons la combinaison cohérente de deux diodes lasers monomodes fibrées émettant à 975 nm via un dispositif externe tout-fibré dont l'architecture est basée sur la géométrie de l'interféromètre de Michelson. Le couplage entre les deux diodes lasers est obtenu en réalisant une rétroaction commune à travers un coupleur fibré 50/50. Nous montrons qu'ainsi le spectre d'émission résultant s'auto-adapte assurant l'émission d'une puissance maximum sur une seule voie du coupleur 50/50

Laser à fibre dopée Erbium multi-longueurs d'ondes

Nous rapportons l'émission simultanée de plusieurs longueurs d'onde dans un même laser à fibre dopée Erbium. Cette émission est réalisée en associant dans la cavité un modulateur acousto-optique permettant de s'affranchir de l'élargissement homogène de la bande de gain et un interféromètre du type Mach-Zehnder qui réalise un filtrage spectral tout en combinant les rayonnements émis par les deux amplificateurs à fibre de l'interféromètre actif

POWER SCALING OF FIBRE LASERS WITH ALL-FIBRE INTERFEROMETRIC CAVITY

International audienc

Génération d'un faisceau à profil photométrique homogène dans une cavité laser à miroir nanostructuré

L'étude concerne la réalisation d'un démonstrateur particulier devant mettre en évidence l'intérêt de composants diffractifs réalisés par stéréolithographie par ondes évanescentes. II s'agit de concevoir un laser UV à excimères émettant un faisceau cohérent de fluence homogène sur une section carrée, l'un des miroirs conventionnels de la cavité étant remplacé par un composant diffractif réfléchissant, nanostructuré suivant son épaisseur et microstructuré suivant ses deux autres dimensions

Potential Role of Sphingolipidoses-Associated Lysosphingolipids in Cancer

Sphingolipids play a key structural role in cellular membranes and/or act as signaling molecules. Inherited defects of their catabolism lead to lysosomal storage diseases called sphingolipidoses. Although progress has been made toward a better understanding of their pathophysiology, several issues still remain unsolved. In particular, whether lysosphingolipids, the deacylated form of sphingolipids, both of which accumulate in these diseases, are simple biomarkers or play an instrumental role is unclear. In the meanwhile, evidence has been provided for a high risk of developing malignancies in patients affected with Gaucher disease, the most common sphingolipidosis. This article aims at analyzing the potential involvement of lysosphingolipids in cancer. Knowledge about lysosphingolipids in the context of lysosomal storage diseases is summarized. Available data on the nature and prevalence of cancers in patients affected with sphingolipidoses are also reviewed. Then, studies investigating the biological effects of lysosphingolipids toward pro or antitumor pathways are discussed. Finally, original findings exploring the role of glucosylsphingosine in the development of melanoma are presented. While this lysosphingolipid may behave like a protumorigenic agent, further investigations in appropriate models are needed to elucidate the role of these peculiar lipids, not only in sphingolipidoses but also in malignant diseases in general