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)

Abstract

We investigated the effect of 5-hydroperoxyeicosatetraenoic acid (5-HPETE) on the PAF formation in Met-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 A, 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 PIP.

Key Words:

• 5-HPETE
• PAF
• fMet-Leu-Phe
• Diacylglycerol
• Protein kinase C
• HL-60 cells