Interferon-gamma-induced differentiation and apoptosis of HT29 cells: dissociation of (glucosyl)ceramide signaling.
Recently, (glyco)sphingolipids (SL) like ceramide (Cer) and glucosylceramide (GlcCer) have been shown to be involved in signaling pathways leading to differentiation and apoptosis in several cell types, including the colon adenocarcinoma cell line HT29. Intracellular levels of Cer can be modulated by ligands such as interferon-gamma (IFN gamma). In the present study we show that IFN gamma, depending on its concentration, has both differentiation- and apoptosis-inducing effects on HT29 cells. Since both phenomena have been related to SL-mediated signaling in other cell types, we next examined whether IFN gamma was able to induce changes in the SL levels of HT29 cells. Remarkably, no significant changes in these levels could be revealed, implying that SL are not involved in IFN gamma-induced differentiation and/or apoptosis of HT29 cells. This observation provides evidence for the hypothesis that SL-mediated signaling pathways might be more cell type specific than is generally assumed.
Veldman
R J
RJ
Department of Physiological Chemistry, University of Groningen, The Netherlands.
Klappe
K
K
Hoekstra
D
D
Kok
J W
JW
D017209:Apoptosis / Q000187:drug effects*; D002272:Carcinoembryonic Antigen / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002518:Ceramides / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D005963:Glucosylceramides / Q000378:metabolism*; D006028:Glycosphingolipids / Q000378:metabolism; D019073:HT29 Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D015398:Signal Transduction / Q000502:physiology*
D002272:Carcinoembryonic Antigen; D002518:Ceramides; D005963:Glucosylceramides; D006028:Glycosphingolipids; D006657:Histones; D007371:Interferon-gamma