The role of sphingolipids in the process of signal transduction

Riboni, Laura; Viani, Paola; Bassi, Rajiv; Prinetti, Alessandro; Tettamanti, Guido

doi:10.1016/s0163-7827(97)00008-8

Cited by 186 publications

(155 citation statements)

References 408 publications

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“…Constitutive degradation of sphingolipids and glycosphingolipids [19,41] takes place in the acidic subcellular compartments, the late endosomes and the lysosomes (Fig. 1).…”

Section: -2 the Sphingosine-ceramide Salvage Pathway In Sphingolipidmentioning

confidence: 99%

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The sphingolipid salvage pathway in ceramide metabolism and signaling

Kitatani

Idkowiak‐Baldys

Hannun

2008

Cellular Signalling

526

457

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Sphingolipids are important components of eukaryotic cells, many of which function as bioactive signaling molecules. Of these, ceramide is a central metabolite and plays key roles in a variety of cellular responses, including regulation of cell growth, viability, differentiation, and senescence. Ceramide is composed of the long-chain sphingoid base, sphingosine, in N-linkage to a variety of acyl groups. Sphingosine serves as the product of sphingolipid catabolism, and it is mostly salvaged through re-acylation, resulting in the generation of ceramide or its derivatives. This recycling of sphingosine is termed the "salvage pathway", and recent evidence points to important roles for this pathway in ceramide metabolism and function. A number of enzymes are involved in the salvage pathway, and these include sphingomyelinases, cerebrosidases, ceramidases, and ceramide synthases. Recent studies suggest that the salvage pathway is not only subject to regulation, but it also modulates the formation of ceramide and subsequent ceramide-dependent cellular signals. This review focuses on the salvage pathway in ceramide metabolism, its regulation, its experimental analysis, and emerging biological functions.

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“…Constitutive degradation of sphingolipids and glycosphingolipids [19,41] takes place in the acidic subcellular compartments, the late endosomes and the lysosomes (Fig. 1).…”

Section: -2 the Sphingosine-ceramide Salvage Pathway In Sphingolipidmentioning

confidence: 99%

“…This latter pathway has been referred to as either sphingolipid recycling or the salvage pathway [16][17][18][19][20][21]. This pathway involves a number of key enzymes that include SMases, possibly glucocerebrosidase (acid-β-glucosidase), ceramidases, and (dihydro)ceramide synthases (Fig.…”

Section: Introductionmentioning

confidence: 99%

The sphingolipid salvage pathway in ceramide metabolism and signaling

Kitatani

Idkowiak‐Baldys

Hannun

2008

Cellular Signalling

526

457

View full text Add to dashboard Cite

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“…Sphingomyelinase-dependent hydrolysis of sphingomyelin and the de novo synthesis are the two major pathways of ceramide biosynthesis (Mathias et al, 1998;Hannun and Luberto, 2000;Riboni et al, 1997;Hannun, 1994) (Figure 2). Sphingomyelinases (SMases) catalyze the hydrolysis of sphingomyelin (ceramidephosphorylcholine) into ceramide and phosphorylcholine (Levade and Jaffrezou, 1999).…”

Section: Ceramide Metabolismmentioning

confidence: 99%

“…Ceramidase catabolizes ceramide to form sphingosine. Ceramide can also be converted to sphingomyelin, glucosyl ceramide, galactosyl ceramide, ceramide-1-phosphate, and ceramide phosphoethanolamine (Hannun and Luberto, 2000;Riboni et al, 1997). De novo ceramide synthesis begins in the endoplasmic reticulum with the serine palmitoyltransferase-catalyzed condensation of serine and palmitoyl-CoA and a subsequent series of reactions produce ceramide on the cytosolic side of the ER ( Mandon et al, 1992;Hirschberg et al, 1993;Michael and Van Echten Deckert G, 1997;Cuvillier et al, 1996).…”

Section: Ceramide Metabolismmentioning

confidence: 99%

Recent advances in the immunobiology of ceramide

Pandey

Murphy

Agrawal

2007

Experimental and Molecular Pathology

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Ceramide, a sphingosine-based lipid molecule, has emerged as a key regulator of a wide spectrum of biological processes such as cellular differentiation, proliferation, apoptosis and senescence. Sphingomyelinase-dependent hydrolysis of sphingomyelin, and de novo synthesis involving the coordinated action of serinepalmitoyl transferase and ceramide synthase, are the two major pathways involved in ceramide synthesis. Clustering of plasma membrane rafts into ceramide enriched platforms serves as an important transmembrane signaling mechanism for cell surface receptors. Ceramides have been implicated in apoptosis, stress-signaling cascades as well as ion channels. There is accumulating evidence that targeted manipulation of ceramide metabolism pathway has immense therapeutic potential and may eventually prove to be a boon in the design of novel strategies and development of innovative treatments for diverse conditions including cardiovascular diseases, cancer and Alzheimer's disease. As yet uncharacterized natural ceramide analogs and novel inhibitors of ceramide metabolism might prove to be potent drugs. In this review, we discuss significant advances that continue to provide intriguing insights into the complex cellular and molecular mechanisms underlying ceramide-mediated signaling cascades.

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“…Ceramide can be generated and consumed by different metabolic routes (41,42,44,45). Ceramide is produced by de novo synthesis in the endoplasmic reticulum or by the hydrolysis of sphingomyelin by acid sphingomyelinases, localized in acidic compartments and neutral sphingomyelinases, and localized in the plasma membrane and mitochondria.…”

mentioning

confidence: 99%

Ceramide-mediated Macroautophagy Involves Inhibition of Protein Kinase B and Up-regulation of Beclin 1

Scarlatti

Bauvy

Ventruti

et al. 2004

Journal of Biological Chemistry

413

376

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The sphingolipid ceramide is involved in the cellular stress response. Here we demonstrate that ceramide controls macroautophagy, a major lysosomal catabolic pathway. Exogenous C 2 -ceramide stimulates macroautophagy (proteolysis and accumulation of autophagic vacuoles) in the human colon cancer HT-29 cells by increasing the endogenous pool of long chain ceramides as demonstrated by the use of the ceramide synthase inhibitor fumonisin B 1 . Ceramide reverted the interleukin 13-dependent inhibition of macroautophagy by interfering with the activation of protein kinase B. In addition, C 2 -ceramide stimulated the expression of the autophagy gene product beclin 1. Ceramide is also the mediator of the tamoxifen-dependent accumulation of autophagic vacuoles in the human breast cancer MCF-7 cells. Monodansylcadaverine staining and electron microscopy showed that this accumulation was abrogated by myriocin, an inhibitor of de novo synthesis ceramide. The tamoxifen-dependent accumulation of vacuoles was mimicked by 1-phenyl-2-decanoylamino-3-morpholino-1-propanol, an inhibitor of glucosylceramide synthase. 1-Phenyl-2-decanoylamino-3-morpholino-1-propanol, tamoxifen, and C 2 -ceramide stimulated the expression of beclin 1, whereas myriocin antagonized the tamoxifendependent up-regulation. Tamoxifen and C 2 -ceramide interfere with the activation of protein kinase B, whereas myriocin relieved the inhibitory effect of tamoxifen. In conclusion, the control of macroautophagy by ceramide provides a novel function for this lipid mediator in a cell process with major biological outcomes.Macroautophagy or autophagy is an evolutionary conserved lysosomal pathway involved in the turnover of long lived proteins and organelles (1-3). Autophagy starts with the formation of a multilayer membrane-bound autophagosome that sequesters fractions of the cytoplasm (4, 5). In mammalian cells, most of autophagosomes receive inputs from endocytic compartments before fusing with lysosomes where the degradation of the sequestered material is completed (6, 7).The physiological importance of autophagy during starvation has been primarily highlighted in rat liver (8) and then in different cell types (reviewed in Refs. 9 and 10). At the same time, the term autophagic cell death or type II programmed cell death (PCD II) has been introduced (11) to describe a cell death different from apoptosis or type I programmed cell death (PCD I) (reviewed in Refs. 12 and 13). The recent progress made in characterization of the molecular mechanism controlling autophagy has brought a renewal of interest for this process (14). There is now evidence for the role of autophagy during development (15-17), in the life span extension (15,18), and in disease such as cancer (19,20), neurodegenerative disease (21, 22), and myopathies (23,24).A family of autophagy-related genes discovered in yeast and almost integrally conserved in all eucaryotic phyla controls the formation of the autophagosome (25). Two conjugation systems (Atg5p-Atg12p and Atg8p lipidation) are involved in...

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The role of sphingolipids in the process of signal transduction

Cited by 186 publications

References 408 publications

The sphingolipid salvage pathway in ceramide metabolism and signaling

The sphingolipid salvage pathway in ceramide metabolism and signaling

Recent advances in the immunobiology of ceramide

Ceramide-mediated Macroautophagy Involves Inhibition of Protein Kinase B and Up-regulation of Beclin 1

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