Céramide

Résumé

vignette|Structure générique d'un céramide. Un céramide est un sphingolipide résultant de la combinaison d'un acide gras avec la sphingosine via une liaison amide. On trouve de telles molécules en abondance dans les membranes cellulaires, où elles entrent notamment dans la constitution des sphingomyélines. Les céramides ne jouent pas qu'un rôle structurel dans les membranes biologiques, et peuvent également revêtir des fonctions de signalisation lipidique. Leurs actions les mieux comprises vont de la différenciation cellulaire à la mort cellulaire programmée (apoptose) en passant par la prolifération cellulaire. Les acides gras qui les constituent ont généralement un nombre pair (de 16 à 24) d'atomes de carbone, sont saturés ou monoinsaturés, et sont souvent α-hydroxylés. La plupart des céramides n'existent pas à l'état naturel si ce n'est comme précurseurs de la biosynthèse des sphingolipides par une réaction d'addition sur la fonction alcool primaire de la sphingosine. Catégor

Source officielle

https://fr.wikipedia.org/wiki/C%C3%A9ramide

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Presentation of selected signalling pathways with emphasis on both the mechanism of action of the molecules involved, molecular interactions and the role of their spatio-temporal organization within the cell, considering cellular dimensions and conditions.

The course covers in detail the interactions of cancer cells with their environment with an emphasis on tumor-angiogenesis, inflammation, adaptive and innate immunity and cancer-induced immune suppression. Additional topics are cancer metabolism, cancer stem cells and metastasis.

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Glycosphingolipid metabolism in cell fate specification

Laura Capolupo, Jaipreet Singh Loomba

Glycosphingolipids (GSLs) are ubiquitous components of eukaryotic plasma membranes that consist of a ceramide backbone linked to a glycan moiety. Both the ceramide and the glycan parts of GSLs display structural variations that result in a remarkable repertoire of diverse compounds. This diversity of GSLs is exploited during embryogenesis, when different GSLs are produced at specific developmental stages and along several differentiation trajectories. Importantly, plasma membrane receptors interact with GSLs to modify their activities. Consequently, two otherwise identical cells can respond differently to the same stimulus owing to their different GSL composition. The metabolic reprograming of GSLs is in fact a necessary part of developmental programs, as its impairment results in developmental failure or tissue-specific defects. Moreover, single-cell variability is emerging as a fundamental player in development: GSL composition displays cell-to-cell variability in syngeneic cell populations owing to the regulatory gene expression circuits involved in microenvironment adaptation and in differentiation. Here, we discuss how GSLs are synthesized and classified and review the role of GSLs in the establishment and maintenance of cell identity. We further highlight the existence of the regulatory circuits that modify GSL pathways and speculate how GSL heterogeneity might contribute to developmental patterning.

2018

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Golgi apparatus (GA) is a center for lipid metabolism and the final target of ceramide pathway, which may result in apoptosis. In this work localization of highly hydrophobic hypericin is followed by time-resolved imaging of NBDC6 (fluorescent ceramide) in U87 MG glioma cells. Decrease of NBDC6 fluorescence lifetimes in cells indicates that hypericin can also follow this pathway. It is known that both, ceramide and hypericin can significantly influence protein kinase C (PKC) activity. Western blotting analysis shows increase of PKC delta autophosphorylation at Ser645 (p(S645) PKC delta) in glioma cells incubated with 500 nM hypericin and confocal-fluorescence microscopy distinguishes p(S645) PKC delta localization between GA related compartments and nucleus. Experimental and numerical methods are combined to study p(S645) PKC delta in U87 MG cell line. Image processing based on conceptual qualitative description is combined with numerical treatment via simple exponential saturation model which describes redistribution of p(S645) PKC delta between nucleus and GA related compartments after hypericin administration. These results suggest, that numerical methods can significantly improve quantification of biomacromolecules (p(S645) PKC delta) directly from the fluorescence images and such obtained outputs are complementary if not equal to typical used methods in biology.

Wiley-V C H Verlag Gmbh2017

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Sphingolipids are not only important components of membranes but also have functions in protein trafficking and intracellular signaling. The LCB1 gene encodes a subunit of the serine palmitoyltransferase, which is responsible for the first step of sphingolipid synthesis. Here, we show that activation of the unfolded protein response (UPR) can restore normal ceramide levels and viability in yeast cells with a conditional defect in LCB1. Dependence on UPR was demonstrated by showing the HAC1-dependence of the suppression. A similar induction of ceramides by UPR seems to take place in mammalian cells. In rat pancreatic INS-1E cells, UPR activation induces the transcription of the CerS6 gene, which encodes a ceramide synthase. This correlates with the specific accumulation of ceramide with a C16 fatty acyl chain upon UPR activation. Therefore, our study reveals a novel connection between UPR induction and ceramide synthesis that seems to be conserved between yeast and mammalian cells.-Epstein, S., C. L. Kirkpatrick, G. A. Castillon, M. Mu iz, I. Riezman, F. P. A. David, C. B. Wollheim, and H. Riezman. Activation of the unfolded protein response pathway causes ceramide accumulation in yeast and INS-1E insulinoma cells. J. Lipid Res. 2012. 53: 412-420.

2012

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