The fatty acid bimodal action on superoxide anion production by human adherent monocytes under phorbol 12-myristate 13-acetate or diacylglycerol activation can be explained by the modulation of protein kinase C and p47phox translocation.
We studied the translocation of protein kinase C (PKC), the endogenous phosphorylation and presence in the membrane fraction of p47phox (the 47-kDa cytosolic component of the phagocyte NADPH oxidase), and the O-.2 production in human adherent monocytes (HAMs). This was performed under phorbol myristate acetate (PMA) or diacylglycerol stimulation after cell preincubation in the presence of either 13-methyltetradecanoate or arachidonate. At 3 nM and 30 microM, both fatty acids had enhancing and depressing effects, respectively, on PKC translocation and O-.2 production strictly depending on the PMA- or diacylglycerol-stimulated state of the cell. Endogenous phosphorylation and membrane presence of p47phox were markedly reinforced in PMA-stimulated HAMs in the presence as compared to the absence of 13-methyltetradecanoate. These results emphasize the fact that in intact cells the capacity of both FAs to potentiate or depress the HAM O-.2 production is mediated by a direct action on the PKC membrane translocation leading to a simultaneous endogenous phosphorylation and membrane translocation of p47phox. They confirm the recent findings (Kadri-Hassani, N., Léger, C. L., and Descomps, B. (1995) J. Lipid Med. Cell Signal. 11, 159-173) on the PKC-mediated, adherent monocyte-specific capacity of these fatty acids and others (with the exception of linear saturated fatty acids) to enhance the PMA-stimulated O-.2 production at nanomolar concentrations and to depress it at micromolar concentrations.
Kadri-Hassani
N
N
Laboratoire de Biologie et Biochimie des Lipides, Unité de Formation et de Rechereche de Médecine, Montpeillier, France.
Léger
C L
CL
Descomps
B
B
D016718:Arachidonic Acid / Q000494:pharmacology; D001798:Blood Proteins / Q000302:isolation & purification / Q000378:metabolism; D002448:Cell Adhesion; D004075:Diglycerides / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology*; D006801:Humans; D007202:Indicators and Reagents; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D009227:Myristic Acids / Q000494:pharmacology*; D009252:NADPH Dehydrogenase / Q000097:blood*; D019255:NADPH Oxidases; D010750:Phosphoproteins / Q000097:blood* / Q000302:isolation & purification; D010766:Phosphorylation; D011493:Protein Kinase C / Q000097:blood*; D013481:Superoxides / Q000097:blood*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D001798:Blood Proteins; D004075:Diglycerides; D005230:Fatty Acids, Nonesterified; D007202:Indicators and Reagents; D009227:Myristic Acids; D010750:Phosphoproteins; D013481:Superoxides; D016718:Arachidonic Acid; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D009252:NADPH Dehydrogenase; D011493:Protein Kinase C; C027331:13-methyltetradecanoic acid; D013755:Tetradecanoylphorbol Acetate