The effect of tumor necrosis factor on the free sphingosine level and sphingomyelinase in murine liver cells and nuclei

: The effects of the human recombinant tumour necrosis factor (TNF) (10 and 40 mg/kg of body mass) on sphingomyelinase activity and sphingosine content in mouse (C57bl) liver cells and nuclei have been studied. Whereas sphingomyelinase is known to be a key enzyme of sphingomyelin metabolism, sphingosine, being a product of deep enzymatic hydrolysis of sphingomyelin, controls the activity of various phosphokinases. The primary response of liver cell to TNF consists in the inhibition of sphingomyelinase; its activation occurs at later periods: after 2 hours at 10 mg/kg TNF and after 4 hours at 40 mg/kg TNF. In the nucleus activation of sphingomyelinase is observed within the first 60 min after TNF administration. Sphingosine accumulation in mouse liver cells and nuclei coincides in time with sphingomyelinase stimulation. In the nuclei activation of the sphingomyelin cycle by TNF is far more pronounced than in the cells, being observed at early periods after TNF injection. A signal mechanism of TNF action on mouse liver cells and nuclei involving a TNF-specific receptor and sphingosine which may activate this receptor phosphorylation is discussed.