Sphingolipid metabolism and signal transduction: inhibition of in vitro phospholipase activity by sphingosine

Franson, Richard C.; Harris, Lesley K.; Ghosh, Shobha; Rosenthal, Miriam D.

doi:10.1016/0167-4889(92)90253-8

Cited by 33 publications

(12 citation statements)

References 41 publications

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“…In our previous studies we reported that SM acts as an inhibitor of various forms of phospholipase A 2 (PLA 2 ) (secretory [52,53] and cytosolic [54]) and thus it plays a protective role in maintaining the integrity of cellular membranes, whereas the product of its degradation, ceramides, are powerful activators of these enzymes [55]. It is supposed that the product of ceramide hydrolysis, sphingosine, also modulates the susceptibility of membrane phospholipids to PLA 2 [56][57][58][59]. However, it is noteworthy that while studies on sphingomyelin and ceramides and their role in cell biology are quite advanced, very little is currently clear about the biophysical properties of sphingosine and sphingosine-1-phosphate, known as second messengers in cell proliferation [7] and survival [60] and as functional participants in the ''CER/S-1-P rheostat" [4].…”

Section: Conclusion and Biological Implicationsmentioning

confidence: 98%

Effect of sphingosine on domain morphology in giant vesicles

Georgieva

Koumanov

Momchilova

et al. 2010

Journal of Colloid and Interface Science

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Section: Conclusion and Biological Implicationsmentioning

confidence: 98%

Effect of sphingosine on domain morphology in giant vesicles

Georgieva

Koumanov

Momchilova

et al. 2010

Journal of Colloid and Interface Science

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“…Several of these lipids cause profound local and long-range effects on the molecular organization and overall topology of the membrane interface (5,20) that can markedly affect lipolytic activity (2,5,10,21). Nonsubstrate lipids such as gangliosides, neutral glycosphingolipids, ceramide (Cer), sphingosine, and semisynthetic derivatives of sphingosine in mixed phospholipid monolayers, unilamellar vesicles, and micelles can modulate the activity of PLA 2 and phospholipase C (2,7,(21)(22)(23)(24)(25)(26).…”

mentioning

confidence: 99%

Surface pressure‐dependent cross‐modulation of sphingomyelinase and phospholipase A₂ in monolayers

Fanani

Maggio

1998

Lipids

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We investigated the ways in which phospholipase A2 and sphingomyelinase are mutually modulated at lipid interfaces. The activity of one enzyme is affected by its own reaction products and by substrates and products of the other enzyme; all this depends differently on the lateral surface pressure. Ceramide inhibits both the sphingomyelinase activity rate and the extent of degradation, and decreases the lag time at all surface pressures. Dilauroyl- and dipalmitoylphosphatidylcholine, the substrates of phospholipase A2 (PLA2), do not affect sphingomyelinase activity. The products of PLA2, palmitic acid and lysopalmitoylphosphatidylcholine, strongly enhance and shift to high surface pressures the activity optimum and the cutoff point of sphingomyelinase. Palmitic acid also shifts to high surface pressures the cut-off point of PLA2 activity. Sphingomyelin strongly inhibits PLA2 at surface pressures above 5 mN/m, while ceramide shifts the cut-off point and the activity optimum to high surface pressures. The sphingolipids increase the lag time of PLA2 at low surface pressures. Both phosphohydrolytic pathways involve different levels of control on precatalytic steps and on the rate of activity that appear independent on specific alterations of molecular packing and surface potential. The mutual lipid-mediated interfacial modulation between both phosphohydrolytic pathways indicates that phospholipid degradation may be self-amplified or dampened depending on subtle changes of surface pressure and composition.

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“…Generation of ROS was measured in unstimulated cells and in cells exposed to increasing concentrations (10 Ϫ11 to 10 Ϫ5 mol/L) of Ang II in the absence and presence of 10 Ϫ5 mol/L diphenylene iodonium (DPI), a flavoprotein inhibitor, 37 or the PLD inhibitor D-erythrosphingosine, dihydro (sphinganine). 38 Cells were pretreated with inhibitors for 15 to 20 minutes before addition of Ang II. Cells were used for single experiments only.…”

Section: Measurement Of Intracellular Rosmentioning

confidence: 99%

Ang II–Stimulated Superoxide Production Is Mediated via Phospholipase D in Human Vascular Smooth Muscle Cells

1999

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Abstract-Intracellular signaling events that mediate the long-term effects of Ang II in vascular smooth muscle cells are unclear, but oxidative stress may play an important role. This study examined the ability of Ang II to generate reactive oxygen species and investigated the putative role of phospholipase D (PLD)-dependent signaling pathways for its production in human vascular smooth muscle cells. In addition, we assessed whether redox-sensitive pathways influence Ang II-stimulated cell growth. Primary and low-passage cells (passages 1 to 4) derived from resistance arteries of subcutaneous gluteal biopsies from healthy subjects were studied. Key Words: oxidative stress Ⅲ superoxide anions Ⅲ intracellular signaling Ⅲ vascular hypertrophy T he multiple actions of Ang II are mediated via highly complex intracellular signaling pathways that are stimulated after binding of the peptide to its cell-surface receptors. 1 The signaling processes are multiphasic, with distinct temporal characteristics. 2 Ang II-induced activation of phospholipase C characteristically occurs within seconds, resulting in increased intracellular free Ca 2ϩ concentration and rapid vascular contraction, 3,4 whereas activation of signaling pathways mediating protein synthesis and cell growth are delayed, occurring within minutes or hours after Ang II stimulation. 2,5 Although the intracellular signaling events underlying Ang II-induced growth are not completely understood, there is increasing evidence suggesting that generation of reactive oxygen species (ROS), such as superoxide anion (⅐O 2 Ϫ ), hydrogen peroxide (H 2 O 2 ), and the reactive hydroxyl radical (⅐OH), may be fundamental in the mitogenic response to this peptide. 6Ϫ8 The major source of ⅐O 2 Ϫ in cardiovascular cells is NADH/ NADPH oxidase, 9Ϫ12 which transfers electrons from NADH or NADPH to molecular oxygen, producing ⅐O 2 Ϫ . The ⅐O 2 Ϫ that is generated by NADH/NADPH oxidase is converted by superoxide dismutase to H 2 O 2 , which is scavenged by catalase or by peroxidases. 13 ⅐O 2 Ϫ and H 2 O 2 stimulate vascular smooth muscle cell (VSMC) hyperplasia and hypertrophy. 6,9,14 These effects are associated with growth-related events such as intracellular alkalinization, increased intracellular free Ca 2ϩ concentration, MAP kinase activation, and induction of proto-oncogene expression. 6,15Ϫ17 Furthermore, antioxidants inhibit cell growth and trigger apoptosis, which implies that a basal level of oxidant stress is necessary for normal cell growth. 18,19 Vascular tissue is constantly exposed to endogenous and exogenous oxidants, which, if unscavenged, may lead to cellular proliferation. ROS concentrations are increased in atherosclerosis, neointimal formation, and hypertension. 20Ϫ22 In Ang II-induced but not catecholamineinduced hypertension, aortic superoxide is increased, which suggests that Ang II-induced effects in hypertension are mediated in part through oxidative stress. 23,24

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Sphingolipid metabolism and signal transduction: inhibition of in vitro phospholipase activity by sphingosine

Cited by 33 publications

References 41 publications

Effect of sphingosine on domain morphology in giant vesicles

Effect of sphingosine on domain morphology in giant vesicles

Surface pressure‐dependent cross‐modulation of sphingomyelinase and phospholipase A₂ in monolayers

Ang II–Stimulated Superoxide Production Is Mediated via Phospholipase D in Human Vascular Smooth Muscle Cells

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Sphingolipid metabolism and signal transduction: inhibition of in vitro phospholipase activity by sphingosine

Cited by 33 publications

References 41 publications

Effect of sphingosine on domain morphology in giant vesicles

Effect of sphingosine on domain morphology in giant vesicles

Surface pressure‐dependent cross‐modulation of sphingomyelinase and phospholipase A2 in monolayers

Ang II–Stimulated Superoxide Production Is Mediated via Phospholipase D in Human Vascular Smooth Muscle Cells

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Surface pressure‐dependent cross‐modulation of sphingomyelinase and phospholipase A₂ in monolayers