Potential role for triglycerides in signal transduction.
We previously reported that endothelin-1 or platelet-derived growth factor promoted in aortic smooth muscle cells a rapid hydrolysis of 1-O-alkyl-2-acyl-sn-glycero-3-phosphoethanolamine (alkyl-PE) which was immediately converted into 1-O-alkyl-2,3-diacyl-sn-glycerol (alkyl-TG) within 5 s or 60 s respectively [C. Comminges et al. (1996) Biochem. Biophys. Res. Commun. 220, 1008-1013 and C. Comminges et al. (1997) Biochim. Biophys. Acta 1355, 69-80]. In this study, we show that this alkyl-PE hydrolysis is triggered by a transient activation of a specific phospholipase C (PLC) regulated by pertussis toxin-sensitive heterotrimeric G-proteins. Moreover, this PLC can be triggered through a Ca2+ influx depending on L-type Ca2+ channel activation, as suggested by the use of a specific 'activator' S(-)-BayK 8644 and of selective inhibitors such as nimodipine. Interestingly, low concentrations (10(-8)-10(-7)M) of alkyl-TG block the opening of L-type Ca2+ channels, whereas identical concentrations of DG do not alter L-type Ca2+ channels. This study thus unravels a hitherto unrecognized signaling pathway generating alkyl-TG as a novel lipid second messenger, potentially acting as a negative feedback regulator of L-type Ca2+ channels.
Maury
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Institut Fédératif de Recherche en Immunologie Cellulaire et Moléculaire, Université Paul Sabatier and INSERM Unité 326, Phospholipides Membranaires, Signalisation Cellulaire et Lipoprotéines, Hôpital Purpan, Toulouse, Fran.
Guérineau
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Comminges
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Mollard
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Prévost
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D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism; D002478:Cells, Cultured; D019332:Endothelin-1 / Q000494:pharmacology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D037342:Pertussis Toxin; D015398:Signal Transduction; D013552:Swine; D014280:Triglycerides / Q000096:biosynthesis / Q000378:metabolism* / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000378:metabolism
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D014280:Triglycerides; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin; D010738:Type C Phospholipases; D020962:Heterotrimeric GTP-Binding Proteins; D002118:Calcium