Salvage of catabolic products in ganglioside metabolism: a study on rat cerebellar granule cells in culture

Riboni, Laura; Bassi, Rajiv; Prinetti, Alessandro; Tettamanti, Guido

doi:10.1016/0014-5793(96)00772-7

Cited by 26 publications

(24 citation statements)

References 35 publications

(55 reference statements)

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“…Thus, we followed the turnover of radiolabeled ceramide and the formation of SM during a chase, after a pulse with [D-erythro-sphingosine-3 H]GM1. The experimental conditions used allowed us to follow the recycling of Sph produced from ganglioside degradation and to determine the fate of ceramide produced from the salvage of catabolically produced Sph (29). The results demonstrate that bFGF did not affect the total amount of radioactivity measured in the organic phase (Fig.…”

Section: Effect Of Bfgf On Ceramide Metabolism From Exogenous and Catmentioning

confidence: 57%

Basic Fibroblast Growth Factor-induced Proliferation of Primary Astrocytes

Riboni

Viani

Bassi

et al. 2001

Journal of Biological Chemistry

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We recently reported that the marked decrease in cellular ceramide in primary astrocytes is an early event associated with the mitogenic activity of basic fibroblast growth factor (bFGF) (Riboni, L., Viani, P., Bassi, R., Stabieini, A., and Tettamanti, G. (2000) GLIA 32, 137-145). Here we show that a rapid activation of sphingomyelin biosynthesis appears to be the major mechanism responsible for the fall in ceramide levels induced by bFGF. When quiescent astrocytes were treated with bFGF, an increased amount of newly synthesized ceramide (from either L-[ 3 H]serine or [ 3 H]sphingosine) was directed toward the biosynthesis of sphingomyelin. Conversely, bFGF did not appear to affect ceramide levels by other metabolic pathways involved in ceramide turnover such as sphingomyelin degradation and ceramide biosynthesis, degradation, and glucosylation. Enzymatic studies demonstrating a relevant and rapid increase in sphingomyelin synthase activity after bFGF treatment have provided a convincing explanation for the activation of sphingomyelin biosynthesis. The bFGF-induced increase in sphingomyelin synthase appears to depend on a post-translational activation mechanism. Moreover, in the presence of brefeldin A, the activation of sphingomyelin biosynthesis was abolished, suggesting that the enzyme is located in a compartment other than the Golgi apparatus. Also the phosphatidylcholine-specific phospholipase C inhibitor D609 exerted a potent inhibitory effect on sphingomyelin biosynthesis. Finally, we demonstrate that inhibition of sphingomyelin biosynthesis by brefeldin A or D609 led to a significant inhibition of bFGF-stimulated mitogenesis. All this supports that, in primary astrocytes, the early activation of sphingomyelin synthase is involved in the bFGF signaling pathway leading to proliferation.Ceramide, a key sphingolipid metabolite in both the biosynthesis and degradation of complex sphingolipids, is involved in the signal transduction of different extracellular stimuli that lead to cell proliferation, cell differentiation, cell cycle arrest, and apoptotic cell death (reviewed in Refs. 1-3). In all these events, the ceramide concentration, possibly at specific subcellular sites, is crucial. There is evidence that different activators such as cytokines, growth factors, and hormones elicit their biological effect by modulating the activity of sphingomyelinases, ceramide synthase, or neutral ceramidase (reviewed in Refs. 1 and 3-5) and thus affect ceramide levels.A role of ceramide as an intracellular mediator of specific extracellular agents has been recognized also in cells from the central nervous system (reviewed in Refs. 6 -8). In neuronal and glial cells, the administration of differentiating or apoptotic agents results in increased cellular levels of ceramide, which, in turn, participate in the cascade of events producing the final effects (9 -12). In a recent study (13), we demonstrated that ceramide plays a role in the growth control of glial cells by basic fibroblast growth factor (bFGF), 1 a factor stimul...

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Section: Effect Of Bfgf On Ceramide Metabolism From Exogenous and Catmentioning

confidence: 57%

Basic Fibroblast Growth Factor-induced Proliferation of Primary Astrocytes

Riboni

Viani

Bassi

et al. 2001

Journal of Biological Chemistry

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“…Exogenous sphingosine is taken up by the cells and is largely utilized for the biosynthesis of complex sphingolipids (10,13,17,43). Sphingolipids have a turnover of hours in neuronal cells (34) and a few days in human fibroblasts (10,44). Thus, after administration of sphingosine to the cells and metabolic labeling of all sphingolipids, in a long chase experiment, sphingosine is produced in the sphingolipid lysosomal catabolism, released from lysosomes, recycled, and only in minor part catabolized to small fragments and water.…”

Section: Discussionmentioning

confidence: 99%

Sphingolipid Uptake by Cultured Cells

Chigorno

Giannotta

Ottico

et al. 2005

Journal of Biological Chemistry

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Human fibroblasts, rat neurons, and murine neuroblastoma cells, cultured in the presence of fetal calf serum, were fed with [1-3 H]sphingosine to radiolabel sphingolipids. The fate of cell sphingolipids, the release of sphingolipids in the culture medium, the interaction of sphingolipids with the proteins and lipoproteins of fetal calf serum, and the fate of sphingolipids taken up by the cells were investigated. For this latter purpose, the culture medium containing radioactive sphingolipids was delivered to nonlabeled cells. The presence of tritium at position 1 of sphingosine allowed us to follow the extent of sphingolipid catabolism by measuring the production of radioactive phosphatidylethanolamine and proteins by recycling the radioactive ethanolamine formed during sphingosine catabolism and the production of tritiated water. We confirmed that in cells the recycling of sphingosine occurred to a high extent and that only a minor portion of cell sphingolipids was catabolized to the small fragments of ethanolamine and water. Cell sphingolipids were released in the culture medium, where they formed large lipoproteic aggregates at a rate of about 12% per day. Released sphingolipids were taken up by the cells and catabolized to the sphingosine and then to ethanolamine, and recycling of sphingosine was not observed. This suggests that in the presence of fetal calf serum in the culture medium, exogenous sphingolipids directly reach the lysosomes, were they are entirely catabolized. Thus, the trafficking of sphingolipids from cells to the extracellular environment and from this to other cells does not allow the modification of the plasma membrane composition.Membrane sphingolipids are complex lipids displaying a strong amphiphilic character (1). This implies an equilibrium between plasma membrane molecules and free monomers present in the extracellular environment. The critical aggregative concentration of sphingolipids is in the nano-or picomolar range (1, 2), thus the amount of free monomers in solution is low. Nevertheless, the quantity of free monomers should increase when a favorable equilibrium leads to the formation of stable lipoprotein complexes (3-5). This process should also occur in living organisms, where significant amounts of sphingolipids are detectable in serum and cerebrospinal fluid from normal and pathological subjects (6 -8), as components of serum lipoproteins or associated with albumin (4).The presence of sphingolipids in biological fluids leads to the following considerations. Exogenous sphingolipids administered to cells are taken up by the cells, thus entering the sphingolipid metabolic pathway. Several studies have been carried out by administering sphingolipids to cells (9). Gangliosides administered to cells that are cultured in the absence of fetal calf serum (FCS) 1 or proteins have been shown to become components of the cell membranes, modifying in some cases the quantity and the quality of plasma membrane gangliosides, and to enter into the endogenous sphingolipid metabolic pathways ...

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“…The production of these two compounds is the only known exit route from the pathways of SL metabolism, since lysosomal degradation of SLs produces SL metabolites that are recycled back into the SL pathway [43], some of which can be subsequently reutilized in the salvage pathway of SL synthesis [44]. Thus, sphingosine formed from ceramide can be recycled back into the pathway of SL synthesis [45] via the action of ceramide synthase, which can use either sphingosine or sphinganine [46]. Study of the lysosomal hydrolysis of SLs and GSLs has been motivated by their involvement in a number of human inherited diseases, the lysosomal storage diseases.…”

Section: Sl Metabolism and Intracellular Transportmentioning

confidence: 98%

The metabolism and function of sphingolipids and glycosphingolipids

Lahiri

Futerman

2007

Cell. Mol. Life Sci.

298

241

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Sphingolipids and glycosphingolipids are emerging as major players in many facets of cell physiology and pathophysiology. We now present an overview of sphingolipid biochemistry and physiology, followed by a brief presentation of recent advances in translational research related to sphingolipids. In discussing sphingolipid biochemistry, we focus on the structure of sphingolipids, and their biosynthetic pathways--the recent identification of most of the enzymes in this pathway has led to significant advances and better characterization of a number of the biosynthetic steps, and the relationship between them. We then discuss some roles of sphingolipids in cell physiology, particularly those of ceramide and sphingosine-1-phosphate, and mention current views about how these lipids act in signal transduction pathways. We end with a discussion of sphingolipids and glycosphingolipids in the etiology and pathology of a number of diseases, such as cancer, immunity, cystic fibrosis, emphysema, diabetes, and sepsis, areas in which sphingolipids are beginning to take a central position, even though many of the details remain to be elucidated.

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Salvage of catabolic products in ganglioside metabolism: a study on rat cerebellar granule cells in culture

Abstract: Cerebellar granule cells in culture were subjected to a pulse (0.5--4 h)-chase (0-4 h) of 10 -

Cited by 26 publications

References 35 publications

Basic Fibroblast Growth Factor-induced Proliferation of Primary Astrocytes

Basic Fibroblast Growth Factor-induced Proliferation of Primary Astrocytes

Sphingolipid Uptake by Cultured Cells

The metabolism and function of sphingolipids and glycosphingolipids

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