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We demonstrate that sphingosylphosphory1choline-mediated cell death involves the activation of different protein kinase C isozymes in different manners. Treating cells with sphingosylphosphorylcholine resulted in activation of protein kinase C delta, which is necessary, together with elevation of Ca2+, for sphingosylphosphorylcholine-induced apoptosis. A rapid translocation from cytosol to membrane, and a proteolytic protein kinase C delta cleavage was found, probably due to activation of caspase-3, to give a catalytically active fragment involved in cellular apoptosis. Moreover, sphingosylphosphory1choline also induced translocation of protein kinase C zeta, resulting in an anti-apoptotic effect. To explore whether a mitochondrial pathway is involved in sphingosylphosphorylcholine-induced apoptosis, we analyzed the effect of sphingosylphosphory1choline on cytochrome c release and caspase-3 activity. We must point out that the sphingolipid caused an increase of cytochrome c release from mitochondria to cytosol concomitantly with an increase of caspase-3 activity. Furthermore, a translocation of Bax was found, after sphingosylphosphory1choline treatment.
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p.443-452,fig.,ref.
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autor
- Departamento de Bioquimica y Biologia Molecular I, Facultad de Quimica, Universidad Complutense de Madrid, 28040 Madrid, Spain
autor
- Departamento de Bioquimica y Biologia Molecular I, Facultad de Quimica, Universidad Complutense de Madrid, 28040 Madrid, Spain
autor
- Departamento de Bioquimica y Biologia Molecular I, Facultad de Quimica, Universidad Complutense de Madrid, 28040 Madrid, Spain
autor
- Departamento de Bioquimica y Biologia Molecular I, Facultad de Quimica, Universidad Complutense de Madrid, 28040 Madrid, Spain
autor
- Departamento de Biologia Molecular, Centro de Biología Molecular Severo Ochoa, CBMSO-UAM, Universidad Autónoma de Madrid, 28049 Madrid, Spain
autor
- Departamento de Bioquimica y Biologia Molecular I, Facultad de Quimica, Universidad Complutense de Madrid, 28040 Madrid, Spain
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PL
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Bibliografia
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bwmeta1.element.agro-477f4a23-6853-4d25-b0b7-8cab47c56a0c