title: Stimulatory and inhibitory actions of lysophosphatidylcholine, depending on its fatty acid residue, on the phospholipase C/Ca2+ system in HL-60 leukaemia cells.
abstract: We examined the mechanism of action of lysophosphatidylcholine (LPC), which is suggested to be involved in the pathogenesis of atherosclerosis and inflammatory disorders, in HL-60 leukaemia cells. Extracellular 1-palmitoyl LPC increased the intracellular Ca2+ concentration in association with production of inositol phosphate. These actions of LPC were markedly inhibited by treatment of the cells with pertussis toxin and U73122, a phospholipase C inhibitor. The lipid-induced stimulation of the phospholipase C/Ca2+ system was also attenuated in the dibutyryl cAMP-induced differentiated (neutrophil-like) cells, in which phospholipase C activation induced by NaF or formyl-Met-Leu-Phe was enhanced. In contrast with the stimulatory action of 1-palmitoyl LPC, 1-stearoyl LPC was inhibitory for the phospholipase C/Ca2+ system stimulated by NaF as well as by 1-palmitoyl LPC or other Ca2+-mobilizing agonists. In a cell-free system, only an inhibitory effect on phospholipase C activity was observed even by 1-palmitoyl LPC; 1-stearoyl LPC was more inhibitive than 1-palmitoyl LPC. Taken together, these results suggest that atherogenic and inflammatory LPC exerts both stimulatory and inhibitory actions on the phospholipase C/Ca2+ system depending on the species of fatty acid residue of the lipid; the stimulatory effect is possibly mediated through G-protein-coupled receptors; the inhibitory effect might be caused by dysfunction of the components involved in the enzyme system owing to the amphiphilic nature of the lipid. 1-Palmitoyl LPC prefers the former receptor stimulation at least in intact cells, but 1-stearoyl LPC preferentially exerts the latter inhibitory action.
authors.affiliation: Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-machi, Maebashi 371-8512, Japan. fokajima@news.sb.gunma-u.ac.jp
authors.forename: F
authors.initials: F
authors.lastname: Okajima
authors.forename: K
authors.initials: K
authors.lastname: Sato
authors.forename: H
authors.initials: H
authors.lastname: Tomura
authors.forename: A
authors.initials: A
authors.lastname: Kuwabara
authors.forename: H
authors.initials: H
authors.lastname: Nochi
authors.forename: K
authors.initials: K
authors.lastname: Tamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Kondo
authors.forename: Y
authors.initials: Y
authors.lastname: Tokumitsu
authors.forename: M
authors.initials: M
authors.lastname: Ui
mesh_terms: D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D002474:Cell-Free System; D004789:Enzyme Activation / Q000187:drug effects; D018922:HL-60 Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008244:Lysophosphatidylcholines / Q000737:chemistry* / Q000494:pharmacology*; D009829:Oleic Acids / Q000737:chemistry; D010169:Palmitic Acids / Q000737:chemistry; D037342:Pertussis Toxin; D013229:Stearic Acids / Q000737:chemistry; D013329:Structure-Activity Relationship; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000187:drug effects*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D008244:Lysophosphatidylcholines; D009829:Oleic Acids; D010169:Palmitic Acids; D013229:Stearic Acids; D010566:Virulence Factors, Bordetella; C006065:We 201; D003994:Bucladesine; D037342:Pertussis Toxin; D010738:Type C Phospholipases; D002118:Calcium