ABSTRACT
Regularities of biologically active lipid metabolites formation in dynamics (5, 10, 30, 60 s) by phorbol 12-miristate 13-acetate stimulation in [14C]palmitic acid have been investigated in normal and leukemia peripheral blood lymphocytes prelabeled with [14C]palmitate. In normal cells there was two-phase formation of 1,2-diacylglycerol (5, 30 s), lysophosphatidylcholine (10, 60 s), as well as free palmitic acid at 10 s of stimulation. Under the identical experimental conditions there was inhibition of investigated lipid release processes at early (5 and 10 s) stages of stimulation of leukemic lymphocytes. At later (30, 60 s) terms of these lymphocytes the activation, basically, similar to norm changes in the formation of palmitic acid-containing metabolites except free palmitic acid (the level of which raised only at 60 second of the post-stimulation) was found. Various protein kinases C are involved in the regulation of investigated lipid levels at certain stages of signal transduction both in norm, and in blast cells. Short-term (5, 10 s) activations of healthy donors lymphocytes are coupled to functioning of Ca2+-independent isoforms of protein kinase C. The inhibition of this protein kinase C in leukemic cells leads to normalization of the investigated lipid release. The data obtained suggests disorders of early membrane-bound reactions in agonist - and a protein kinase C-mediated processes of formation palmitic acid-containing lipid metabolites in the leukemic cells in comparison with the norm.
