[Change in the level of sphingosine in rat liver nuclei and cells during oncogene superexpression induced by cycloheximide].

Changes in the sphingosine content in rat liver cells and nuclei have been studied with reference to the level of nuclear oncogene expression, induced by cycloheximide (0.1, 0.5 and 3.0 mg/kg). It has been found that only the sublethal (3 mg/kg) dose of cycloheximide which induces the superexpression of c-fos and c-myc oncogenes can promote sphingosine accumulation in the cell. At the moment of enhanced expression of nuclear oncogenes, the maximum content of free sphingosine exceeds the control level 1.5- and 3-fold in the cell and in the nuclei, respectively. The difference in the sphingosine accumulation patterns in the cell and in the nuclei testifies to the fact that sphingomyelin metabolism is more active in the nuclei than in the cell. Sphingosine accumulation in the nuclei is characterized by coordination of sphingomyelinase activity and changes in the sphingomyelin content. A comparative analysis of activities of enzymes of sphingomyelin (sphingomyelinase) and phosphatidyl inositol (phosphatidyl inositol kinase) cycles indicates that in the nuclei the activation of the sphingomyelin cycle forestalls the cycloheximide-induced activation of the phosphatidyl inositol cycle and the maximal accumulation of nuclear oncogene mRNAs. A model of activation of oncogene expression with participation of sphingosine inhibiting protein kinase C and activating casein kinase II, the key enzymes of the signal transduction system of cell proliferation and differentiation, is proposed.