guanosine-5--o-(2-thiodiphosphate) and Lymphoma--Large-B-Cell--Diffuse

Permeabilized human leukemia HL-60 and U-937 cells suspended in an acidic or alkaline medium release various unsaturated fatty acids, most abundantly oleic and arachidonic acids. Concomitant production of lysophospholipids suggests that phospholipases A2 play a major role in this fatty acid release reaction. The fatty acid release at acidic conditions depends on the intracellular Ca2+ concentrations at the 10(-8)-10(-7) M range and is enhanced by membrane-permeant diacylglycerols, although this enhancement seems independent of protein kinase C activation. On the other hand, the fatty acid release at alkaline conditions is potentiated by vanadate, and this potentiation is counteracted by genistein, suggesting a role of tyrosine phosphorylation in this release reaction. GTP[gamma S], an activator of G proteins, greatly enhances the fatty acid release. Aluminum fluoride, another activator of heterotrimeric G proteins, also greatly potentiates this release reaction. Phorbol ester increases the fatty acid release at alkaline conditions, to some extent, whereas it counteracts the vanadate-induced potentiation of fatty acid release. The results imply that several phospholipases A2 are coupled to receptors for their activation, thereby functioning in the transmembrane control of cellular events.

Topics: Calcium; Cell Line; Cell Membrane Permeability; Diglycerides; Electroporation; Fatty Acids, Nonesterified; Genistein; Guanosine 5'-O-(3-Thiotriphosphate); Guanosine Diphosphate; Homeostasis; Humans; Hydrogen-Ion Concentration; Isoflavones; Kinetics; Leukemia, Promyelocytic, Acute; Lymphoma, Large B-Cell, Diffuse; Phospholipases A; Phospholipases A2; Protein-Tyrosine Kinases; Signal Transduction; Sodium Fluoride; Tetradecanoylphorbol Acetate; Thionucleotides; Tumor Cells, Cultured; Vanadates