Modulation of phosphatidylserine homeostasis by amphiphilic cations in a human neuronal cell line, LA-N-2.
The stimulatory effects of sphingosine and oleylamine upon the incorporation of [3H]serine into its corresponding phospholipid, phosphatidylserine, by LA-N-2 cell cultures, have been reported (Singh et al. (1992) FEBS Lett., 296, 166-168). The presence of chlorpromazine and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) in cultures of these cells provoked increased phosphatidylserine synthesis but decreased protein synthesis in a concentration-dependent fashion. Several other amphiphilic cations, including dimethyldidodecylammonium bromide, verapamil, desipramine, amitriptyline, and mepacrine also stimulated phosphatidylserine synthesis in a dose-dependent manner. These amphiphilic cations reduced the conversion of phosphatidylserine to phosphatidylethanolamine. The observed stimulation of phosphatidylserine synthesis by amphiphilic cations was unaltered in protein kinase C (PKC) down-regulated cells and in retinoic acid (RA)-induced differentiated cells. In contrast, bis(2-ethylhexyl)hydrogen phosphate, an amphiphilic anion, strongly inhibited the incorporation of [3H]serine into phosphatidylserine. These observations demonstrate that phosphatidylserine synthesis in LA-N-2 cells can be modulated by amphiphilic cations and anions. It is suggested that the amphiphilic cations cause the ethanolamine moiety of membrane bound phosphatidylethanolamine to become more accessible to the juxtaposed serine base exchange enzyme.
Singh
I N
IN
Department of Biochemistry and Molecular Biology, University of Manitoba, Winnipeg, Canada.
Massarelli
R
R
Kanfer
J N
JN
D000838:Anions / Q000494:pharmacology*; D002412:Cations / Q000494:pharmacology*; D002460:Cell Line; D002746:Chlorpromazine / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D008055:Lipids / Q000032:analysis; D009419:Nerve Tissue Proteins / Q000032:analysis; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010718:Phosphatidylserines / Q000378:metabolism*; D011493:Protein Kinase C / Q000187:drug effects; D012995:Solubility; D013449:Sulfonamides / Q000494:pharmacology; D014867:Water / Q000737:chemistry
D000838:Anions; D002412:Cations; D008055:Lipids; D009419:Nerve Tissue Proteins; D010718:Phosphatidylserines; D013449:Sulfonamides; D014867:Water; C017967:W 7; D011493:Protein Kinase C; D002746:Chlorpromazine