Data di Pubblicazione:
2007
Citazione:
Metabolic and functional role of the ceramide binding protein CERT in glioma cells / P. Giussani, T. Colleoni, R. Bassi, L. Brioschi, G. Tettamanti, K. Hanada, L. Riboni, P. Viani. - In: NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY. - ISSN 0028-1298. - 374:4(2007 Jan), pp. 328-329. ((Intervento presentato al 5. convegno International Meeting of the Sphingolipid Club tenutosi a Calella de la Costa nel 2006 [10.1007/s00210-006-0116-8].
Abstract:
Different studies demonstrate that in glial cells ceramide
(Cer) exerts antiproliferative and proapoptotic effects, and
strongly support that Cer-signalling is altered in glial
tumors. The control of ceramide levels in glial cells
involves specific enzymes which are known to be localized
in different subcellular compartments as well as Cer
movements along the sphingomyelin biosynthetic pathway.
A key element in defining the role of Cer in sphingolipid
metabolism and signalling is its hydrophobic nature, and its
consequent inability to spontaneously move among
different subcellular sites where the enzymes of its
metabolism and its molecular targets are located. Based on
this evidence, the biological effect exerted by Cer may
depend on the presence of specific signalling pools of this
bioactive sphingoid in the cell, as well as the regulation of
its intracellular traffic. Recently, the identification in CHO
cells of the Cer specific carrier protein CERT have revealed
a novel pathway for the delivery of Cer to the Golgi
apparatus for sphingomyelin biosynthesis. In this study we
investigated the metabolic and functional role of CERT in
glioma cells. All glioma cells analyzed constitutively
express CERT, the protein being mainly associated to thecytosolic fraction. Metabolic experiments performed with
different radioactive metabolic precursors of sphigolipids
indicate that, in all analyzed glioma cells, downregulation
of CERT by RNA interference technology promoted a
significant but not complete reduction of the amount of
Cer converted to SM. This suggests that in glioma cells
CERT mediated Cer transport contributes in addressing
ceramide toward sphingomyelin biosynthesis. Since the
regulation of sphingomyelin biosynthesis represents a
crucial step in the role of ceramide on glial cell
proliferation we evaluated the possible role of CERT in the
control of glioma cell proliferation. We found that in all
glioma cells down regulation of CERT resulted in an
increased cell proliferation associated to higher ERK1/2
phosphorylation. In vitro and in vivo experiments indicated
that CERT is necessary for the inhibition exerted by Cer on
ERK activation. In conclusion these results suggest that
CERT, besides the involvement in sphingolipid metabolism,
participates to Cer signalling and could play a role in the
control of glioma cell proliferation.
Tipologia IRIS:
01 - Articolo su periodico
Elenco autori:
P. Giussani, T. Colleoni, R. Bassi, L. Brioschi, G. Tettamanti, K. Hanada, L. Riboni, P. Viani
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