Sphingosine and phorbol ester modulate protein kinase C activity and modify ATP-evoked calcium mobilization in glioma C6 cells.
The effect of sphingosine and 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on ATP-evoked Ca(2+) mobilization in glioma C6 cells was studied with the Fura-2 video-imaging technique. Treatment of the cells with TPA, an activator of protein kinase C, reduced the ATP-evoked release of Ca(2+) from the intracellular stores, whereas sphingosine, known from in vitro studies as a protein kinase C inhibitor, potentiated Ca(2+) release synergistically with ATP. ATP-induced Ca(2+) mobilization was also enhanced by a specific protein kinase C inhibitor, GF 109203X. Pretreatment of the cells with GF 109203X prevented TPA action, whereas TPA diminished the stimulatory effect of sphingosine. However, this sphingosine effect was only observed after a short (1 min) treatment, whereas a longer treatment (5 min) reduced ATP-evoked Ca(2+) release. It is therefore concluded that sphingosine has two apparent actions: it inhibits protein kinase C providing a positive feedback regulation of receptor signals and it releases Ca(2+) from intracellular stores by an unknown mechanism, possibly independent of protein kinase C.
Department of Molecular and Cellular Neurobiology, Nencki Institute of Experimental Biology, 3 Pasteur Street, Warsaw, 02-093, Poland.
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Czajkowski
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Barańska
D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005910:Glioma / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D007211:Indoles / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D013110:Sphingosine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D019284:Thapsigargin / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000378:metabolism
D007211:Indoles; D008301:Maleimides; D019284:Thapsigargin; D000255:Adenosine Triphosphate; D011493:Protein Kinase C; D010738:Type C Phospholipases; C070515:bisindolylmaleimide I; D013110:Sphingosine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium