Decreased phospholipase D (PLD) activity in ceramide-induced apoptosis of human keratinocyte cell line HaCaT

The Journal of Investigative Dermatology
Y Iwasaki-BesshoY Nozawa

Abstract

Ceramide is recognized as an intracellular lipid second messenger, which induces various kinds of cell function including apoptosis. To evaluate the competence of ceramide on the keratinocyte apoptosis, we examined effects of a cell-permeable ceramide, N-acetylsphingosine (C2-ceramide), on a human keratinocyte cell line, HaCaT. C2-ceramide induced a distinct apoptosis in HaCaT cells in a time-dependent manner, as inferred by morphologic hallmarks of apoptosis such as bleb formation, cell body shrinkage, nuclear chromatin condensation, and internucleosomal DNA fragmentation. In sharp contrast, an inactive C2-ceramide, dihydroC2-ceramide, which lacks the 4-5trans double bond, failed to induce the apoptosis. The apoptotic HaCaT cells induced by C2-ceramide showed a significant suppression of phospholipase D (PLD) activity, regardless of the presence or absence of guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS). This indicates that C2-ceramide inhibits both GTPgammaS dependent and GTPgammaS independent PLD. The membrane associated GTPgammaS dependent PLD activity was stimulated by recombinant adenosine diphosphate-ribosylation factor. The adenosine diphosphate-ribosylation factor dependent and independent PLD activities were inhibi...Continue Reading

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Citations

Mar 31, 2004·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Mark McDermottAndrew J Morris

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Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis