RESUMEN
Earlier studies showed that treatment of LA-N-1 cells with TPA, a tumoral promoter, leads to the stimulation of a G protein-regulated phospholipase D (PLD) in the nuclei. Now we demonstrate that retinoic acid, a cellular differentiation inducing agent, activates a nuclear oleate-dependent PLD in LA-N-1 cells. Treatment of the nuclei with retinoic acid induces the breakdown of phosphatidylcholine (PtdCho). Our results indicate that PLD is regulated differentially depending on the nature of the stimulatory agent. These results strongly suggest the existence of two nuclear PLD isoforms in LA-N-1 nuclei that hydrolyze PtdCho.
Asunto(s)
Núcleo Celular/enzimología , Ácido Oléico/farmacología , Fosfolipasa D/metabolismo , Tretinoina/farmacología , Núcleo Celular/efectos de los fármacos , Núcleo Celular/metabolismo , Diglicéridos/metabolismo , Activación Enzimática , Glicerofosfolípidos/metabolismo , Humanos , Neuroblastoma , Ácidos Fosfatidicos/metabolismo , Fosfatidilcolinas/metabolismo , Fosfolipasa D/clasificación , Células Tumorales CultivadasRESUMEN
Compound 24, an alkyl-substituted amino acid amide, previously found to activate pertussis toxin-sensitive G proteins in cell membranes and membrane protein fractions, was used as a tool to determine the mechanism/location of nicotine inhibition of amyloid beta peptide-stimulated phospholipase A2 and D activities in a human neuroblastoma cell line, LA-N-2, in vitro. In contrast to our previous findings with amyloid beta peptide, these phospholipase activations by compound 24 were not inhibited by (-)-nicotine, cholera toxin or tetanus toxin pretreatment. The contrasting activation of these phospholipases by amyloid beta peptide and compound 24 are discussed.