5-Hydroperoxyeicosatetraenoic acid (5-HPETE) enhances the synthesis of 1-O-alkyl-2-sn-acetyl-glycero-3-phosphocholine (PAF) in fMet-Leu-Phe-stimulated HL-60 cells: key role of diacylglycerol (DAG) in activation of protein kinase C (PKC).
We investigated the effect of 5-hydroperoxyeicosatetraenoic acid (5-HPETE) on the PAF formation in fMet-Leu-Phe-stimulated HL-60 cells. 5-HPETE was found to enhance the PAF synthesis in fmlp-stimulated cells without causing additional mobilization of intracellular calcium. However, a significant increase in diacylglycerol (DAG) levels due to 5-HPETE was observed, which in turn activated the protein kinase C (PKC). Obviously, PKC is responsible for the activation of phospholipase A2 and the release of lyso-PAF and AA from complex lipid stores. Further, the dose-dependent increase in DAG production in absence of simultaneous increase in total inositol phosphates is indicative of an additional source for DAG besides PIP2.
Nigam
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Department of Gynecological Endocrinology, Universitätsklinikum Steglitz, Free University Berlin, W. Germany.
Müller
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D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D004075:Diglycerides / Q000378:metabolism / Q000502:physiology*; D004121:Dimethyl Sulfoxide; D004789:Enzyme Activation; D005989:Glycerides; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D015289:Leukotrienes / Q000494:pharmacology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000096:biosynthesis* / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*
D004075:Diglycerides; D005989:Glycerides; D007295:Inositol Phosphates; D015289:Leukotrienes; D010972:Platelet Activating Factor; D009240:N-Formylmethionine Leucyl-Phenylalanine; C025348:arachidonic acid 5-hydroperoxide; D011493:Protein Kinase C; D002118:Calcium; D004121:Dimethyl Sulfoxide