1,25 dihydroxyvitamin D(3) activates sphingomyelin turnover in ROS17/2.8 osteosarcoma cells without sphingolipid-induced changes in cytosolic Ca(2+).
1,25-Dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] initiates the hydrolysis of sphingomyelin in ROS 17/2.8 osteosarcoma cells with the resultant generation of cell-associated ceramide. Increases in ceramide levels were detectable at 15 min and maximal one hour after exposure of cells to 1,25(OH)(2)D(3). Neither 1,25(OH)(2)D(3) nor exogenous ceramide elicited a change in cytosolic free Ca(2+) ([Ca(2+)](i)). Transient elevations in [Ca(2+)](i) were observed when cells were exposed to exogenous sphingosine, but there was no detectable conversion of ceramide to sphingosine in 1, 25(OH)(2)D(3)-treated cells. Ceramide also did not stimulate Ca(2+) uptake across ROS 17/2.8 cell plasma membranes. Collectively, these results suggest that 1,25(OH)(2)D(3) activates sphingomyelin turnover in ROS 17/2.8 osteosarcoma cells but that the sphingolipid metabolite ceramide is not responsible for 1,25(OH)(2)D(3)-induced activation of plasma membrane Ca(2+) channels.
Liu
R
R
Department of Biological Sciences, University of Delaware, Newark, Delaware, USA.
Xu
Y
Y
Farach-Carson
M C
MC
Vogel
J J
JJ
Karin
N J
NJ
D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002518:Ceramides / Q000378:metabolism / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D006868:Hydrolysis / Q000187:drug effects; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D012516:Osteosarcoma / Q000378:metabolism* / Q000473:pathology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D013109:Sphingomyelins / Q000378:metabolism*; D013110:Sphingosine / Q000378:metabolism / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D020746:Calcium Channels, L-Type; D002518:Ceramides; D013109:Sphingomyelins; D004533:Egtazic Acid; D002117:Calcitriol; D013110:Sphingosine; D011188:Potassium; D002118:Calcium