TY - JOUR
T1 - Ceramide in nitric oxide inhibition of glioma cell growth
T2 - Evidence for the involvement of ceramide traffic
AU - Viani, Paola
AU - Giussani, Paola
AU - Brioschi, Loredana
AU - Bassi, Rosaria
AU - Anelli, Viviana
AU - Tettamanti, Guido
AU - Riboni, Laura
PY - 2003/3/14
Y1 - 2003/3/14
N2 - The treatment of C6 glioma cells with the nitric oxide donor, PAPANONOate ((Z)-[N-(3-ammoniopropyl)-N-(n-propyl)amino]diazen-1-ium-1,2-diolate), resulted in a dose-dependent inhibition of cell proliferation. This was associated to a rapid and significant increase of ceramide levels and was mimicked by treatments that augment cellular ceramide. Metabolic experiments with radioactive sphingosine, serine, and choline showed that nitric oxide strongly reduced the utilization of ceramide for the biosynthesis of both sphingomyelin and glucosylceramide. Nevertheless, nitric oxide did not modify the activity of different enzymes of ceramide metabolism. The possibility that nitric oxide impairs the availability of ceramide for sphingolipid biosynthesis was then investigated. The metabolism of N-hexanoyl-[3H]sphingosine demonstrated that nitric oxide did not affect the biosynthesis of N-hexanoyl-[3H]sphingolipids but inhibited the metabolic utilization of long chain [3H]ceramide, synthesized in the endoplasmic reticulum (ER) from the recycled [3H]sphingosine. Moreover, results obtained with fluorescent ceramides, brefeldin A, ATP depletion, as well as in a ceramide transport assay indicate that nitric oxide impairs the traffic of ceramide from ER to Golgi apparatus. All this supports that, in glioma cells, the modulation of ceramide traffic can contribute to the regulation of its intracellular levels and participate in the nitric oxide-activated signaling pathway involved in the control of cell proliferation.
AB - The treatment of C6 glioma cells with the nitric oxide donor, PAPANONOate ((Z)-[N-(3-ammoniopropyl)-N-(n-propyl)amino]diazen-1-ium-1,2-diolate), resulted in a dose-dependent inhibition of cell proliferation. This was associated to a rapid and significant increase of ceramide levels and was mimicked by treatments that augment cellular ceramide. Metabolic experiments with radioactive sphingosine, serine, and choline showed that nitric oxide strongly reduced the utilization of ceramide for the biosynthesis of both sphingomyelin and glucosylceramide. Nevertheless, nitric oxide did not modify the activity of different enzymes of ceramide metabolism. The possibility that nitric oxide impairs the availability of ceramide for sphingolipid biosynthesis was then investigated. The metabolism of N-hexanoyl-[3H]sphingosine demonstrated that nitric oxide did not affect the biosynthesis of N-hexanoyl-[3H]sphingolipids but inhibited the metabolic utilization of long chain [3H]ceramide, synthesized in the endoplasmic reticulum (ER) from the recycled [3H]sphingosine. Moreover, results obtained with fluorescent ceramides, brefeldin A, ATP depletion, as well as in a ceramide transport assay indicate that nitric oxide impairs the traffic of ceramide from ER to Golgi apparatus. All this supports that, in glioma cells, the modulation of ceramide traffic can contribute to the regulation of its intracellular levels and participate in the nitric oxide-activated signaling pathway involved in the control of cell proliferation.
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U2 - 10.1074/jbc.M207729200
DO - 10.1074/jbc.M207729200
M3 - Article
C2 - 12515829
AN - SCOPUS:0038322046
VL - 278
SP - 9592
EP - 9601
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 11
ER -