The role of ceramide (Cer) as lipid mediator governing the fate of glioma cells is supported by the evidence that the modulation of Cer levels in these cells plays a fundamental role in the control of cell proliferation, differentiation and apoptosis. A key element in defining the role of Cer in cell signaling 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. In this context a crucial step is Cer transport from the ER, where it is synthesized, to the Golgi, the primary subcellular site for the biosynthesis of sphingomyelin (SM) and glucosylceramide. Cer metabolism was studied in two different human glioma cell lines: astrocytoma cells (CCF-STTG1) and glioblastoma cells (T98G) characterized by a different proliferating capacity in culture. In T98G and CCF cells the metabolic machinery devoted to newly synthesized Cer processing is different, T98G possessing an higher capacity to synthesize glycolipids compared to CCF, but CCF have an higher capacity to synthesize SM. Among the molecules that can regulate growth, differentiation and apoptosis, nitric oxide (NO) has emerged as a key element in its role as an inter- and intra-cellular mediator in the nervous system. NO treatment results in a significant increase of Cer levels paralleled by a reduction of SM in CCF but not in T98G cells. Results obtained using fluorescent Cers show that treatment of the cells with NO alters the ER-to-Golgi trafficking of Cer in CCF cells but not in T98G. These data support that in the two different glioma cell lines used, NO has a different effect on Cer availability for SM biosynthesis, supporting the hypothesis of differences in the mechanism for ER-to-Golgi trafficking of Cer. It will be intriguing to investigate the possible role of intracellular levels of Cer and NO in pathways involved in the control of cell proliferation.
|Titolo:||Nitric oxide modulates ceramide traffic in human glioma cells : a fluorescence microscopy study|
|Parole Chiave:||Ceramide ; glioma cells ; lipid transport ; fluorescence microscopy|
|Settore Scientifico Disciplinare:||Settore BIO/10 - Biochimica|
Settore BIO/12 - Biochimica Clinica e Biologia Molecolare Clinica
|Data di pubblicazione:||2005|
|Tipologia:||Book Part (author)|
|Appare nelle tipologie:||03 - Contributo in volume|