Ceramide inhibition of phospholipase D and its relationship to RhoA and ARF1 translocation in GTPγS-stimulated polymorphonuclear leukocytes

Mansfield, Parnela J.; Carey, Shannon S.; Hinkovska‐Galcheva, Vania; Shayman, James A.; Boxer, Laurence A.

doi:10.1182/blood-2002-11-3341

Cited by 18 publications

(13 citation statements)

References 37 publications

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“…Such a control of PLD1 expression by ceramide has been observed in other cell systems such as C6 glial cells and RBL-2H3 mast cells undergoing apoptosis under C2-ceramide treatment (Nakashima and Nozawa, 1999). In addition, ceramide regulates PLD at the level of enzymatic activity, such a regulation being observed in cell-free systems (Singh et al, 2001;Venable et al, 1996;Abousalham et al, 1997;Mansfield et al, 2004). PLD inhibition might result from ceramide inhibition of the translocation of PLD-activating factors such as PKC␣ (Jones and Murray, 1995;Abousalham et al, 1997), PKC␤1, ADP-ribosylation factor 1 (ARF1), Cdc42 and RhoA (Abousalham et al, 1997), from inhibition of PKC interaction with ARF-activated PLD (Venable et al, 1996) or from a direct interaction of ceramide with the catalytic core of PLDs (Singh et al, 2001).…”

Section: Discussionmentioning

confidence: 81%

Inhibition of de novo ceramide synthesis upregulates phospholipase D and enhances myogenic differentiation

Mébarek

Komati

Naro

et al. 2007

Journal of Cell Science

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In L6 skeletal myoblasts induced to differentiate by Arg8-vasopressin treatment, a short-lived lowering of ceramide levels was observed, followed by a long-lasting elevation that was prevented by inhibitors of the de novo synthesis pathway, fumonisin B1 and myriocin. Both inhibitors increased the expression of myogenic differentiation markers and cell fusion rate, whereas short-chain ceramides inhibited these responses. Similar drug effects were observed on primary mouse satellite cell differentiation. Furthermore, bacterial sphingomyelinase overexpression suppressed myogenin nuclear accumulation in L6 cells. These data suggested that endogenous ceramide mediates a negative feedback mechanism limiting myogenic differentiation, and that inhibitors of ceramide synthesis promoted myogenesis by removing this control. Phospholipase D (PLD), a recognized target of ceramide, is required for myogenesis, as shown by the negative effects of PLD1 isoform depletion obtained by siRNA treatment. Fumonisin induced an increase in PLD activity of L6 cells, whereas C6-ceramide decreased it. The expression of PLD1 mRNA transcripts was selectively decreased by C6-ceramide, and increased by ceramide synthesis inhibitors. An early step of myogenic response is the PLD1-dependent formation of actin stress fiber-like structures. C6-ceramide addition or overexpression of sphingomyelinase impaired actin fiber formation. Ceramide might thus regulate myogenesis through downregulation of PLD1 expression and activity.

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Section: Discussionmentioning

confidence: 81%

Inhibition of de novo ceramide synthesis upregulates phospholipase D and enhances myogenic differentiation

Mébarek

Komati

Naro

et al. 2007

Journal of Cell Science

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“…Lactosylceramide, an abundant ceramide metabolite, can be loaded into differentiated HL-60 cells to induce migration (36). By contrast, ceramide was shown to modulate many other effector functions, including the production of cytokines and reactive oxygen intermediates, phagocytosis, b2 integrin expression, degranulation, and apoptosis (8,13,(37)(38)(39).…”

Section: Discussionmentioning

confidence: 99%

An Obligate Role for Membrane-Associated Neutral Sphingomyelinase Activity in Orienting Chemotactic Migration of Human Neutrophils

Sitrin¹,

Sassanella²,

Petty³

2011

Am J Respir Cell Mol Biol

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“…Recent progress has increased our understanding on the functional roles of Cer, Sph, and S1P in mast cell responsiveness (17), in the priming and inactivation of neutrophils and macrophages (42)(43)(44)(45)(46)(47), and in the chemotactic motility of various immune cells (25, 28 -30, 48). Other studies have underscored the importance of sphingolipids in additional immune cell processes such as differentiation of monocytes into macrophage or granulocyte lineages (49,50), regulation of apoptotic cell death and survival of lymphocytes (51) and macrophages (52), overall suggesting a role of these lipids in the regulation of various physiological aspects of immune cell function.…”

Section: Concluding Remarks and Future Prospectsmentioning

confidence: 99%

Sphingolipids and the Balancing of Immune Cell Function: Lessons from the Mast Cell

Olivera

Rivera

2005

The Journal of Immunology

114

109

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Recent studies reveal that metabolites of sphingomyelin are critically important for initiation and maintenance of diverse aspects of immune cell activation and function. The conversion of sphingomyelin to ceramide, sphingosine, or sphingosine-1-phosphate (S1P) provides interconvertible metabolites with distinct biological activities. Whereas ceramide and sphingosine function to induce apoptosis and to dampen mast cell responsiveness, S1P functions as a chemoattractant and can up-regulate some effector responses. Many of the S1P effects are mediated through S1P receptor family members (S1P1–5). S1P1, which is required for thymocyte emigration and lymphocyte recirculation, is also essential for Ag-induced mast cell chemotaxis, whereas S1P2 is important for mast cell degranulation. S1P is released to the extracellular milieu by Ag-stimulated mast cells, enhancing inflammatory cell functions. Modulation of S1P receptor expression profiles, and of enzymes involved in sphingolipid metabolism, particularly sphingosine kinases, are key in balancing mast cell and immune cell responses. Current efforts are unraveling the complex underlying mechanisms regulating the sphingolipid pathway. Pharmacological intervention of these key processes may hold promise for controlling unwanted immune responses.

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Ceramide inhibition of phospholipase D and its relationship to RhoA and ARF1 translocation in GTPγS-stimulated polymorphonuclear leukocytes

Cited by 18 publications

References 37 publications

Inhibition of de novo ceramide synthesis upregulates phospholipase D and enhances myogenic differentiation

Inhibition of de novo ceramide synthesis upregulates phospholipase D and enhances myogenic differentiation

An Obligate Role for Membrane-Associated Neutral Sphingomyelinase Activity in Orienting Chemotactic Migration of Human Neutrophils

Sphingolipids and the Balancing of Immune Cell Function: Lessons from the Mast Cell

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