Basic fibroblast growth factor-induced proliferation of primary astrocytes- Evidence for the involvement of sphingomyelin biosynthesis

Citation
L. Riboni et al., Basic fibroblast growth factor-induced proliferation of primary astrocytes- Evidence for the involvement of sphingomyelin biosynthesis, J BIOL CHEM, 276(16), 2001, pp. 12797-12804
Citations number
73
Categorie Soggetti
Biochemistry & Biophysics
Journal title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN journal
00219258 → ACNP
Volume
276
Issue
16
Year of publication
2001
Pages
12797 - 12804
Database
ISI
SICI code
0021-9258(20010420)276:16<12797:BFGFPO>2.0.ZU;2-I
Abstract
We recently reported that the marked decrease in cellular ceramide in prima ry astrocytes is an early event associated with the mitogenic activity of b asic fibroblast growth factor (bFGF) (Riboni, L,, Viani, P,, Bassi, R,, Sta bieini, A., and Tettamanti, G, (2000) GLIA 32, 137-145), Here we show that a rapid activation of sphingomyelin biosynthesis appears to be the major me chanism responsible for the fall in ceramide levels induced by bFGF, When q uiescent astrocytes were treated with bFGF, an increased amount of newly sy nthesized ceramide (from either L-[H-3]serine or [H-3]sphingosine) was dire cted toward the biosynthesis of sphingomyelin, Conversely, bFGF did not app ear to affect ceramide levels by other metabolic pathways involved in ceram ide turnover such as sphingomyelin degradation and ceramide biosynthesis, d egradation, and glucosylation, Enzymatic studies demonstrating a relevant a nd rapid increase in sphingomyelin synthase activity after bFGF treatment h ave provided a convincing explanation for the activation of sphingomyelin b iosynthesis, The bFGF-induced increase in sphingomyelin synthase appears to depend on a post-translational activation mechanism. Moreover, in the pres ence of brefeldin A, the activation of sphingomyelin biosynthesis was aboli shed, suggesting that the enzyme is located in a compartment other than the Golgi apparatus. Also the phosphatidylcholine-specific phospholipase C inh ibitor D609 exerted a potent inhibitory effect on sphingomyelin biosynthesi s. Finally, we demonstrate that inhibition of sphingomyelin biosynthesis by brefeldin A or D609 led to a significant inhibition of bFGF-stimulated mit ogenesis. All this supports that, in primary astrocytes, the early activati on of sphingomyelin synthase is involved in the bFGF signaling pathway lead ing to proliferation.