Ceramide traffic in C6 glioma cells: Evidence for CERT-dependent and independent transport from ER to the Golgi apparatus

Giussani, Paola; Colleoni, T.; Brioschi, L.; Bassi, Rajiv; Hanada, Kentaro; Tettamanti, Guido; Riboni, Laura; Viani, Paola

doi:10.1016/j.bbalip.2007.11.002

Cited by 30 publications

(40 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…43 were used. C6 glioma cells plated at 3 ϫ 10 4 cell/cm 2 were maintained 24 h in DMEM plus 10% FCS and then transfected in the same medium with a 1:1 (by mol) mix of S87 ϩ S522 (si-CERT) or the nontargeting corresponding sequences (sicontrol) using Lipofectamine 2000 according to the manufacturer's protocol.…”

Section: Methodsmentioning

confidence: 99%

“…The relative intensities of bands were quantified by densitometry. CERT immunoblotting was performed using si-control and si-CERT transfected cells lysed with CERT buffer (10 mM Tris-HCl, pH 7.4, 0.25 mM sucrose, 0.5 mM phenylmethylsulfonyl fluoride, 10 g/ml aprotinin, 5 g/ml leupeptin, 5 g/ml pepstatin), processed, and analyzed as described previously (43). 6 -Cer in absolute ethanol were prepared and added to fresh medium.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Phosphatidylinositol 3-Kinase/AKT Pathway Regulates the Endoplasmic Reticulum to Golgi Traffic of Ceramide in Glioma Cells

Giussani¹,

Brioschi²,

Bassi

et al. 2009

Journal of Biological Chemistry

View full text Add to dashboard Cite

World Health Organization classifies gliomas according to their cellular features and their grade of malignancy (from I to IV) (4). Glioblastoma multiforme (GBM), 3 also referred to as grade IV astrocytoma, is the most frequent class of malignant primary brain tumor and one of the most aggressive forms of cancer. There is a poor prognosis for patients with GBM, the median survival being 9 -12 months, and this does not significantly improve even after aggressive treatment with multiple approaches, including surgery, chemotherapy, and radiotherapy (5). This poor survival rate seems to be mainly due to the marked invasiveness and proliferation of GBM, as well as to their apoptotic resistance and aberrant angiogenesis. These malignancy features could be related to the varying mutations frequently found in GBM tumors that impact different key pathways involved in the control of cell proliferation, survival, differentiation, migration, and DNA repair (6 -9).Among the disregulated signaling pathways in GBMs, PI3K-Akt-PTEN has been identified as being an important oncogenic pathway (10 -12). PI3Ks are members of a unique and conserved family of lipid kinases that phosphorylate the 3Ј-hydroxyl group of phosphatidylinositol and phosphoinositides such as phosphatidylinositol(4,5)P 2 (PIP 2 ), which is converted to phosphatidylinositol(3,4,5)P 3 (PIP 3 ). The activation of PI3Ks can occur through growth factor receptors, G-protein-coupled receptors, cell adhesion molecules, and oncogenes such as Ras. The generated polyphosphoinositides bind to the pleckstrin homology (PH) domain of different proteins, including PDK1 * This work was supported by grants from the University of Milan (to P. G., L. R., and P. V.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. N-[hexanoyl-6-3 H]D-erythro-hexanoyl-sphingosine; HPTLC, high performance thin layer chromatography; NBD-C 6 -Cer, 6-((N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)hexanoyl) sphingosine; FAPP, four phosphate adaptor protein; EGF-FAPP1-PH, PH domain of FAPP1 protein fused with enhanced green fluorescent protein; DN-AKT, dominant negative mutant of Akt; PBS, phosphate-buffered

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Phosphatidylinositol 3-Kinase/AKT Pathway Regulates the Endoplasmic Reticulum to Golgi Traffic of Ceramide in Glioma Cells

Giussani¹,

Brioschi²,

Bassi

et al. 2009

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…39 Whether the ceramide transported through this route can reach alternative pools of SMS in the Golgi apparatus (i.e., early Golgi) is a fascinating still open question.…”

Section: Discovery Of a Ceramide Transfer Protein With A Key Role In mentioning

confidence: 99%

Tales and Mysteries of the Enigmatic Sphingomyelin Synthase Family

Holthuis

Luberto

2010

Advances in Experimental Medicine and Biology

View full text Add to dashboard Cite

In the last five years tremendous progress has been made toward the understanding of the mechanisms that govern sphingomyelin (SM) synthesis in animal cells. In line with the complexity of most biological processes, also in the case of SM biosynthesis, the more we learn the more enigmatic and finely tuned the system appears. Therefore with this review we aim first, at highlighting the most significant discoveries that advanced our knowledge and understanding of SM biosynthesis, starting from the discovery of SM to the identification of the enzymes responsible for its production; and second, at discussing old and new riddles that such discoveries pose to current investigators.

show abstract

“…Similarly to SM, efficient de novo synthesis of glycosphingolipids is dependent on CERT (Hanada et al 2003;Halter et al 2007). In contrast, the synthesis of glycosphingolipids from sphingosine is largely independent of CERT (D'Angelo et al 2007; Giussani et al 2008), and thus probably relies on vesicular trafficking of ceramide from the ER to the Golgi. The synthesis of most glycosphingolipids begins by the addition of a glucosyl moiety to a ceramide on the cytosolic side of Golgi membranes.…”

Section: Glycosphingolipidsmentioning

confidence: 99%

“…Sphingosine can reenter the salvage pathway by being acylated in the ER to form ceramide. The reutilization of sphingosine for the synthesis of GSLs is largely independent of CERT, suggesting that this pathway relies on vesicular trafficking of ceramide from the ER to the Golgi apparatus (D'Angelo et al 2007;Giussani et al 2008). Sphingosine destined for degradation must first be phosphorylated to sphingosine-1-phosphate, which is then hydrolyzed to phosphoethanolamine and hexadecenal by a sphingosine-1-phosphate lyase in the ER (Ikeda et al 2004).…”

Section: Sphingolipid Recyclingmentioning

confidence: 99%