Melittin Stimulates Incorporation and Degradation of Sphingomyelin in Synaptosomal Plasma Membranes

Pellkofer, R.; Marsh, Derek; Hoffmann-Bleihauer, P.; Sandhoff, Konrad

doi:10.1111/j.1471-4159.1982.tb07895.x

Cited by 11 publications

(6 citation statements)

References 14 publications

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“…3A, the addition of 10 μM desipramine almost completely counteracted the effect induced by 5 μM anandamide, and markedly reduced that observed with 10 μM. In addition, treatment of Chang liver cells with melittin, a non-specific activator of sphingomyelinase (26), induced an apoptotic effect like that observed in cells treated with anandamide. The effect was dosedependent so that cell viability was reduced by approximately 65% after 24 h of treatment with melittin at a concentration of 500 ng/ml (Fig.…”

Section: Involvement Of Ceramide and Oxidative Stress In Anandamideinmentioning

confidence: 83%

Anandamide-induced apoptosis in Chang liver cells involves ceramide and JNK/AP-1 pathway

Giuliano

Calvaruso²,

Pellerito³

et al. 2006

Int J Mol Med

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Abstract. In the present study we demonstrate that anandamide, the most important endogenous cannabinoid, markedly induced apoptosis in Chang liver cells, an immortalized nontumor cell line derived from normal liver tissue, while it induced only modest effects in a number of hepatoma cell lines. The apoptotic effect was reduced by methyl-ß-cyclodextrin, a membrane cholesterol depletor, suggesting an interaction between anandamide and the membrane microdomains named lipid rafts. Anandamide effects were mediated by the production of ceramide, as demonstrated by experiments performed with the sphingomyelinase inhibitor, desipramine, or with the sphingomyelinase activator, melittin. This conclusion was confirmed by the observation that exogenous C2-ceramide induced a remarkable apoptotic effect in the same cells. Anandamide-induced apoptosis in Chang liver cells involved oxidative stress and activation of p38/JNK pathway, which was accompanied by a remarkable increase in AP-1 DNA-binding activity. Moreover, the levels of both c-Jun and JunB, two components of the AP-1 complex, and those of FasL and Bim, two transcriptional targets of AP-1, also increased during anandamide treatment. In addition, anandamide increased the level of Bax and caused degradation of full-length Bid with the production of the active truncated form. These effects were accompanied by dissipation of mitochondrial transmembrane potential with the consequent activation of both caspase-3 and caspase-6. On the contrary, in hepatoma cells, anandamide did not induce apoptotic effects and it was not possible to observe any increase in p38/JNK pathway and AP-1 activity after drug treatment. Our results suggest that the induction of cell death in nontumor Chang liver cells by anandamide was mediated by ceramide, JNK and AP-1 and was dependent on the activation of both the extrinsic and intrinsic pathways of apoptosis.

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Section: Involvement Of Ceramide and Oxidative Stress In Anandamideinmentioning

confidence: 83%

Anandamide-induced apoptosis in Chang liver cells involves ceramide and JNK/AP-1 pathway

Giuliano

Calvaruso²,

Pellerito³

et al. 2006

Int J Mol Med

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“…Melittin influences the permeability properties of membranes [6][7][8][9][10] and affects the activity of membrane bound enzymes [11][12][13]. The nature of its interaction with phospholipid model membranes has been extensively investigated (for reviews, see Refs.…”

Section: Introductionmentioning

confidence: 99%

Melittin induces HII phase formation in cardiolipin model membranes

Batenburg

Hibbeln

Verkleij

et al. 1987

Biochimica et Biophysica Acta (BBA) - Biomembranes

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The interaction of melittin with bovine heart cardiolipin model membranes was investigated via binding assays, 3t P-NMR, freeze-fracture electron microscopy, small angle X-ray diffraction and fluorescence based fusion assays. A strong binding (K d < 10-7 M) appeared to be accompanied by the formation of large structures, resulting from a fusion process of extremely fast initial rate. As the melittin content is increased, bilayer structure is gradually lost and from a cardiolipin to melittin ratio of about 6 the lipid starts to organize itself in an hexagonal H ii phase. At lower temperatures (T < 40 ° C) the coexistence of another structure is observed, characterized by a broad isotropic 31p-NMR signal and giving rise to sharp X-ray reflections, most probably a cubic phase, as suggested also by freeze-fracture images, showing orderly stacked particles. The results are discussed in relation to contrasting observations on the structural changes induced by melittin in the zwitterionic phospholipid system of dipalmitoylphosphatidylcholine (Dufourcq, J. et al. (1986) Biochim. Biophys. Acta 859, 33-48). The biological relevance of the observations with respect to the process of protein insertion into membranes is indicated.

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“…Such peptides possess a hydrophobic region that is inserted into the membrane, displacing an interior part of the phospholipid bilayer leaflet and thereby altering the permeability of the membrane. In doing so, melittin is also able to increase phospholipase activity (Batenburg, 1988;Carrasco, 1987;Gelehter & Rozengurt, 1980;Katsu et al, 1989;Pellkofer et al, 1982;Walenga, 1980). The release of choline or phosphorylcholine could therefore result from the modifications made to the membrane by a viral protein that leads to disruption of the phospholipid bilayer, allowing the release from the cellular pool of molecules such as small metabolites and potassium ions Carrasco & Smith, 1976).…”

Section: Discussionmentioning

confidence: 99%

“…However, this seems not to be the case since poliovirus is able to induce cytopathic effects and cell rounding by activating only phospholipase C, with no activation of phospholipase A2 (Guinea et al, 1989). Of course, apart from the activation of phospholipase C, poliovirus might disturb the integrity of the membrane by a mechanism similar to that of other lytic proteins such as melittin (Batenburg, 1988;Carrasco, 1987;Gelehter & Rozengurt, 1980;Katsu et al, 1989;Pellkofer et al, 1982;Walenga, 1980). Such peptides possess a hydrophobic region that is inserted into the membrane, displacing an interior part of the phospholipid bilayer leaflet and thereby altering the permeability of the membrane.…”

Section: Discussionmentioning

confidence: 99%

Enhancement of phospholipase activity during poliovirus infection

Irurzun

Pérez

Carrasco

1993

Journal of General Virology

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Infection of human cells with poliovirus leads to modification of phospholipase activity. Phospholipase C, which generates inositol triphosphate, is stimulated, whereas the activation of phospholipase A2 by the calcium ionophore A23187 is inhibited. Analysis of phospholipid moieties in media of HeLa cells infected with poliovirus indicates that the release of fatty acids is not enhanced during infection, suggesting that phospholipase A1 and A2 activities are not stimulated. The release of choline into the medium is significantly higher 3 h after infection, indicating that a phospholipase that has phosphatidylcholine as its substrate becomes acti-

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Melittin Stimulates Incorporation and Degradation of Sphingomyelin in Synaptosomal Plasma Membranes

Cited by 11 publications

References 14 publications

Anandamide-induced apoptosis in Chang liver cells involves ceramide and JNK/AP-1 pathway

Anandamide-induced apoptosis in Chang liver cells involves ceramide and JNK/AP-1 pathway

Melittin induces HII phase formation in cardiolipin model membranes

Enhancement of phospholipase activity during poliovirus infection

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