1,721,106 research outputs found
Reassociation of eukaryotic ribosomal subunits and polyamine concentration in Yoshida ascites hepatoma and Ehrlich ascites carcinoma cells during growth
No full textThe activity on ribosome monomers of dissociation factor preparations obtained by high salt wash from ribosomes and from the post-ribosomal supernatant (cytosol) of Yoshida rat ascites hepatoma and Ehrlich mouse ascites carcinoma cells and from the liver of control and tumor-bearing animals has been determined at different periods of intraperitoneal tumor growth. The concentration of the polyamines spermine, spermidine and putrescine has also been measured under the same conditions. Results here reported show the presence of an association factor activity on subunit ribosomes at low Mg2+ concentrations in the post-ribosomal supernatant fractions of Yoshida ascites hepatoma and Ehrlich ascites carcinoma cells during tumor growth. An association factor activity also takes place in the ribosomal high salt wash extracts of Yoshida ascites cells at the terminal stages of tumor growth. Since an increase of spermidine to putrescine ratios occurs during tumor growth the changes in the rate of ribosome monomer dissociation into units here observed might be attributable, at least in part, to changes in polyamine concentrations under the conditions studied
Ceramide in primary astrocytes from cerebellum : metabolism and role in cell proliferation
No full textCerebellar astrocytes are equipped with an efficient molecular machinery able to control the levels, and possibly the subcellular location, of ceramide. The major metabolic routes that contribute to the maintenance and variation of the cellular ceramide include ceramide biosynthesis, by de novo pathway or sphingosine recycling, ceramide formation from complex sphingolipids degradation and ceramide catabolism. In cerebellar astrocytes from rat cerebellum a peculiar metabolism of sphingomyelin occurs. This includes the preponderance of acidic sphingomyelinase, paralleled by a deficiency of the neutral Mg2+-dependent enzyme, as well as the presence of an extra-Golgi form of sphingomyelin synthase, which shares many characteristics with PC-PLC. Moreover these cells are characterized by a high efficiency in converting sphingosine to ceramide, possibly functional to the role played by astrocytes in the prevention of neuronal damage by high sphingosine concentration. Recent evidence demonstrates that a change of ceramide level is one of the key steps in the chain of reactions elicited by mitogenic stimuli. In fact, low cellular levels of ceramide characterize, and appear to be required for, the proliferation of cerebellar astrocytes. In particular mitogenic stimuli, such as basic fibroblast growth factor (bFGF), rapidly down regulate the cellular levels of ceramide by stimulating sphingomyelin synthase. Ceramide acts as an intracellular physiological inhibitor of cell growth, being able to counteract the effect of bFGF by inhibiting the MAP kinase pathway. Although many questions remain in this field, the present knowledge strongly supports that ceramide represents a crucial member within lipid mediators, involved in the signaling pathways underlying cell proliferation in cerebellar astrocytes
Reassociation of eukaryotic ribosomal subunits by a factor from rat ascites hepatoma cytosol
No full textPost-ribosomal supernatant extracts from Yoshida AH 130 ascites hepatoma cells promote the in vitro association of ribosomal subunits at low Mg2+ concentration. Comparable extracts from rat liver show, on the contrary, dissociation factor activity on ribosome monomers
Role of ceramide and sphingosine-1-phosphate in the regulation of glioma cell death and survival
No full textSphingosine -1-phosphate in the tumor niche promotes glioblastoma malignancy
No full textGlioblastoma (GBM) is the most frequent and lethal brain tumor, and is characterized by not only the presence of cancer cells but also a considerable amount of parenchymal cells. Among them, microglia and endothelial cells are recognized as crucial for both tumor growth and spread. However, the signals regulating the interplay between different cells in the GBM niche are little known. The sphingolipid metabolite sphingosine-1-phosphate (S1P) has emerged as a crucial factor in promoting GBM growth, invasion, and drug-resistance, through interaction with its specific receptors. Notwithstanding, its cellular origin in the GBM niche remains only partially known. In this study we investigated the capacity of microglia and endothelial cells of the GBM niche to act as source and/or target of S1P. We found that different cells of the GBM microenvironment, including GBM-derived tumor cells, stem cells, and endothelial cells, as well as microglia are all able to rapidly synthesize and secrete S1P. Among different cell types, GBM stem cells and GBM-derived endothelial cells were found to be particularly effective in releasing newly synthesized S1P extracellularly. Further experiments revealed that after co-culture, GBM and parenchymal cells exhibit enhanced expression of S1P receptors, and of sphingosine kinase (leading to increased S1P secretion), respectively. In addition, we found that extracellular S1P is able to induce multiple effects on different cells, by promoting growth, stemness and survival of tumor cells, migration and vasculogenesis of endothelial cells, and inflammatory properties of microglia. In conclusion, our data demonstrate that different cell types of the GBM niche and their cross-talk contribute to the S1P enrichment of the GBM microenvironment, where S1P prompts multiple processes which favor GBM progression and malignancy
Predominance of the acylation route in the metabolic processing of exogenous sphingosine in neural and extraneural cells in culture
No full textThe metabolic fate of exogenous [H-3]sphingosine was investigated in five types of cultured cells: primary cultures of neurons and astrocytes, murine and human neuroblastoma cells and human skin fibroblasts. After administration of 40 nM [3-H-3]sphingosine into a cell-conditioned medium containing fetal calf serum, all cell types rapidly and efficiently incorporated the long-chain base in a time-dependent fashion. In all cases, after a 120 min pulse, the amount of radioactivity taken up was in the range of the endogenous sphingosine content. However, unchanged [H-3]sphingosine represented only a very minor portion of the label incorporated into cells throughout the pulse period (10-120 min), indicating rapid and efficient sphingosine metabolism in these cells. Most of the [H-3]sphingosine taken up was metabolically processed, either by degradation (assessed as (H2O)-H-3 release into the culture medium) or by N-acylation (mainly to radioactive ceramide, sphingomyelin, neutral glycolipids and gangliosides). [H-3]Sphingosine 1-phosphate accounted for less than 2 % of the total radioactivity incorporated in all cases. Throughout the pulse period and in all cell types, H-3-labelled organic metabolites largely prevailed over (H2O)-H-3, indicating that N-acylation is the major metabolic fate of sphingosine in these cells under apparently physiological conditions. These results are consistent with the notion that sphingosine has a rapid turnover in the cells studied, and indicate that regulation of the basal level of this bioactive molecule occurs mainly through N-acylation
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