TNF-ALPHA-INDUCED AEROBIC SYNTHESIS OF ATP ON PLASMA-MEMBRANES OF TARGET-CELLS - THE RELATION TO THE EXPRESSION OF THE NUCLEAR ONCOGENE C-MYC

The accumulation of ATP by preparations of plasma membranes enriched p articles (PMEP) isolated from rat hepatocytes, murine splenocytes and human T-lymphocytes has been investigated after the binding of human a nd murine tumour necrosis factors (TNF alpha) to their specific recept ors. The TNF alpha-induced expression of the nuclear oncogene c-myc in intact hepatocytes has been also studied. TNF alpha induced the marke d biosynthesis of ATP on PMEP of hepatocytes and splenocytes within th e first minute of incubation. The biosynthesis of ATP was independent of the activity of adenylate kinase and only occured in the presence o f all the components of aerobic phosphorylation and the electron accep tor, cytochrome C or diferric transferrin. The level of ATP on PM corr elated with the degree of expression of the nuclear oncogene c-myc in the same target cells. Adriamycin totally suppressed the biosynthesis of ATP on PM and simultaneously inhibited the expression of c-myc. The ATP synthesized on PM is suggested to be involved in transduction of the proliferative or growth signal to the cell nucleus.