title: Nuclear sphingomyelin pathway in serum deprivation-induced apoptosis of embryonic hippocampal cells.
abstract: Sphingomyelin (SM) cycle has been involved in the regulation of proliferation, differentiation, and apoptosis. Increases in ceramide have been found after a larger number of apoptotic stimuli including cytokines, cytotoxic drugs, and environmental stresses. Accumulating evidence suggest that the subcellular localization of ceramide generation is a critical factor in determining the cellular behavior. Since recently enzymes involved in ceramide metabolism such as sphingomyelinase, SM synthase, sphingosine kinase and ceramidase have been found in the nucleus of hepatocyte cells, we have studied first the presence and the physicochemical characteristics of SM metabolism enzymes in nuclei isolated from embryonic hippocampal cells (cell line HN9.10e). The activities of sphingomyelinase and SM-synthase have been assayed and the ceramide production evaluated at different times after serum deprivation in these neurones cultivated in serum-deficient medium. We report that both enzymes are present in the nucleus of embryonic hippocampal cells and differ from those present in the homogenate in optimum pH. After serum deprivation, that induces a time-dependent decrease in cell viability and increase of the cell percentage in G1 phase of the cell cycle, a nuclear sphingomyelinase activation together with SM-synthase inhibition and a consequent increase of nuclear ceramide pool have been demonstrated. No similar enzyme activity modifications in homogenate have been identified. The possible role of nuclear sphingomyelinase/sphingomyelin-synthase balance in serum deprivation-induced apoptosis in the embryonic hippocampal cell is discussed.
authors: Department of Clinic and Experimental Medicine, Physiopathology, Policlinico Monteluce, Perugia, Italy.
authors: Elisabetta
authors: E
authors: Albi
authors: Samuela
authors: S
authors: Cataldi
authors: Elisa
authors: E
authors: Bartoccini
authors: Mariapia Viola
authors: MV
authors: Magni
authors: Francesca
authors: F
authors: Marini
authors: Francesca
authors: F
authors: Mazzoni
authors: Giuseppe
authors: G
authors: Rainaldi
authors: Monica
authors: M
authors: Evangelista
authors: Mercedes
authors: M
authors: Garcia-Gil
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002453:Cell Cycle / Q000502:physiology; D002467:Cell Nucleus / Q000737:chemistry / Q000201:enzymology*; D002470:Cell Survival; D002478:Cells, Cultured; D003470:Culture Media / Q000737:chemistry*; D004622:Embryo, Mammalian / Q000033:anatomy & histology*; D004625:Embryo, Nonmammalian; D006624:Hippocampus / Q000166:cytology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D044967:Serum / Q000378:metabolism*; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism; D013109:Sphingomyelins / Q000378:metabolism*; D017855:Transferases (Other Substituted Phosphate Groups) / Q000378:metabolism
chemical_list: D003470:Culture Media; D013109:Sphingomyelins; D017855:Transferases (Other Substituted Phosphate Groups); C070186:phosphatidylcholine-ceramide phosphocholine transferase; D013108:Sphingomyelin Phosphodiesterase