Sphingolipids

Shayman, James A.

doi:10.1046/j.1523-1755.2000.00136.x

Cited by 56 publications

(39 citation statements)

References 163 publications

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“…It is worth mentioning in this context that, in some systems, ceramide acts concomitantly with a lowering of intracellular Ca# + [35]. Conversely, the rise of sphingosine is usually accompanied by an increase in the intracellular Ca# + concentration [20,34,40,41]. These two facts are in accordance with the dual role, reported here, that these sphingolipids have with respect to the Ca# + -ATPase.…”

Section: Discussionsupporting

confidence: 84%

“…Since it has been reported that ceramide in many biological systems acts antagonistically with sphingosine [19,21,33,34], we next studied the effect of this ceramide derivative on the Ca# + -ATPase activity. Interestingly, enzyme activity was inhibited by sphingosine in a dose-dependent manner ( Figure 5).…”

Section: Figure 2 Effects Of Ceramide and Cam On Ca 2 + -Atpase's Affmentioning

confidence: 99%

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Ceramide and sphingosine have an antagonistic effect on the plasma-membrane Ca2+-ATPase from human erythrocytes

2002

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The plasma-membrane Ca# + -ATPase is a key enzyme in the regulation of the intracellular Ca# + concentration. On the other hand, sphingolipids have been recognized recently as important second messengers, acting in many systems in combination with Ca# + . In view of the fact that the Ca# + -ATPase is stimulated by ethanol, and since sphingolipids possess free hydroxy groups, we decided to study the possible effect of ceramide and sphingosine on this calcium pump. Here we show that ceramide stimulates the Ca# + -ATPase in a dose-dependent manner and additively to the activation observed in the presence of calmodulin or ethanol, when compared with any of these effectors added alone. Ceramide affects both the affinity for Ca# + and the V max of the enzyme. Furthermore, this second messenger also stimulates Ca# +

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Section: Discussionsupporting

confidence: 84%

Section: Figure 2 Effects Of Ceramide and Cam On Ca 2 + -Atpase's Affmentioning

confidence: 99%

Ceramide and sphingosine have an antagonistic effect on the plasma-membrane Ca2+-ATPase from human erythrocytes

2002

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“…Sphingolipids are important signaling molecules in a variety of biologic contexts (1)(2)(3). Sphingosine 1-phosphate, in one paradigm, binds to members of a family of G protein-coupled receptors (S1P [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15] ) triggering diverse effects including proliferation, survival, migration, morphogenesis, adhesion molecule expression, and cytoskeletal changes (4 -8).…”

mentioning

confidence: 99%

Expression of the Sphingosine 1-Phosphate Receptor, S1P1, on T-cells Controls Thymic Emigration

Allende

Dreier

Mandala

et al. 2004

Journal of Biological Chemistry

415

381

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S1P 1 is a widely distributed G protein-coupled receptor whose ligand, sphingosine 1-phosphate, is present in high concentrations in the blood. The sphingosine 1-phosphate receptor-signaling pathway is believed to have potent effects on cell trafficking in the immune system. To determine the precise role of the S1P 1 receptor on T-cells, we established a T-cell-specific S1P 1 knock-out mouse. The mutant mice showed a block in the egress of mature T-cells into the periphery. The expression of the S1P 1 receptor was up-regulated in mature thymocytes, and its deletion altered the chemotactic responses of thymocytes to sphingosine 1-phosphate. The results indicated that the expression of the S1P 1 receptor on T-cells controls their exit from the thymus and entry into the blood and, thus, has a central role in regulating the numbers of peripheral T-cells.Sphingolipids are important signaling molecules in a variety of biologic contexts (1-3). Sphingosine 1-phosphate, in one paradigm, binds to members of a family of G protein-coupled receptors (S1P 1-15 ) triggering diverse effects including proliferation, survival, migration, morphogenesis, adhesion molecule expression, and cytoskeletal changes (4 -8).S1P 1 /Edg 1 , the first of these receptors described (9, 10), couples to a G i pathway. During embryonic development, the S1P 1 receptor is highly expressed in the vascular system. Gene disruption in mice has demonstrated an essential function of the S1P 1 receptor in endothelial cells for the formation of a stable vascular network (11,12).The S1P 1 receptor is widely expressed in the adult, in particular in endothelial cells, the brain, and the heart, and also in the cells of the immune system (13, 14). S1P 1 and S1P 4 receptors have been detected in T-lymphocytes (15-17). Stimulation of receptor signaling has been found to mediate and regulate cell migration and suppress proliferation and cytokine production (17, 18). Recently, S1P 1 receptors have also been implicated in lymphocyte trafficking and homing as the result of studies using FTY720, a potent immunosuppressive agent. FTY720, a sphingosine analogue, is phosphorylated by sphingosine kinase type I and more efficiently by sphingosine kinase type II (19 -21) and functions as an agonist ligand for S1P 1 , S1P 3 , S1P 4 , and S1P 5 receptors (19,22). FTY720 causes lymphopenia through sequestration of circulating lymphocytes within lymph nodes and Peyer's patches (19,(22)(23)(24) and also blocks the egress of T-cells from the thymus (25, 26). However, it is not known at which S1P receptor and cell type FTY720 exerts its effects.To begin to address the physiologic function of the S1P 1 receptor and sphingosine 1-phosphate signaling in T-cells, we have generated a T-cell-specific mouse knock-out of the S1P 1 receptor using the Cre/loxP system. Our results with these mice reveal a crucial role for the S1P 1 receptor in the egress of mature T-cells from the thymus into the circulation. EXPERIMENTAL PROCEDURESGeneration of the S1P 1 loxP/loxP Lck-Cre Mice-We previously g...

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“…In yeast there are two types of LCBs, dihydrosphingosine (DHS) and phytosphingosine (PHS), which have a carbon chain length of 18 to 20 (C-18-20). Mammals have sphingosine (predominantly C-18 [17]) as their major sphingoid base, although they also make small amounts of DHS and PHS [27]. In Drosophila and other dipterans, the sphingoid bases are not C-18, but rather C-14 and C-16 [28,29].…”

Section: Structural Overview and Biosynthesis Of Sphingolipidsmentioning

confidence: 99%

“…In addition, complex sphingolipids were shown to act as receptors to permit the entry of microorganisms into the cell and to alter the sensitivity of cells to cell-surface ligands [13][14][15]. Sphingolipid metabolites also facilitate cellular processes such as cell division, differentiation, and cell death [2,[16][17][18]. The relative concentrations of sphingolipid metabolites are thought to be regulated tightly, because each of them could have a different effect on cells.…”

Section: Introductionmentioning

confidence: 99%

Sphingolipids and membrane biology as determined from genetic models

Rao

Acharya

2008

Prostaglandins & Other Lipid Mediators

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The importance of sphingolipids in membrane biology was appreciated early in the twentieth century when several human inborn errors of metabolism were linked to defects in sphingolipid degradation. The past two decades have seen an explosion of information linking sphingolipids with cellular processes. Studies have unraveled mechanistic details of the sphingolipid metabolic pathways, and these findings are being exploited in the development of novel therapies, some now in clinical trials. Pioneering work in yeast has laid the foundation for identifying genes encoding the enzymes of the pathways. The advent of the era of genomics and bioinformatics has led to the identification of homologous genes in other species and the subsequent creation of animal knock-out lines for these genes. Discoveries from these efforts have re-kindled interest in the role of sphingolipids in membrane biology. This review highlights some of the recent advances in understanding sphingolipids' roles in membrane biology as determined from genetic models.

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Sphingolipids

Cited by 56 publications

References 163 publications

Ceramide and sphingosine have an antagonistic effect on the plasma-membrane Ca2+-ATPase from human erythrocytes

Ceramide and sphingosine have an antagonistic effect on the plasma-membrane Ca2+-ATPase from human erythrocytes

Expression of the Sphingosine 1-Phosphate Receptor, S1P1, on T-cells Controls Thymic Emigration

Sphingolipids and membrane biology as determined from genetic models

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