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Simultaneous activation of p38 and JNK by arachidonic acid stimulates the cytosolic phospholipase A 2-dependent synthesis of lipid droplets in human monocytes

AutorGuijas, Carlos ; Pérez-Chacón, Gema ; Astudillo, Alma M. ; Rubio, Julio M. ; Gil-de-Gómez, Luis ; Balboa, María A. ; Balsinde, Jesús
Palabras claveLipid mediators
Arachidonic acid
Fecha de publicación2012
EditorAmerican Society for Biochemistry and Molecular Biology
CitaciónJournal of Lipid Research 53(11): 2343-2354 (2012)
ResumenExposure of human peripheral blood monocytes to free arachidonic acid (AA) results in the rapid induction of lipid droplet (LD) formation by these cells. This effect appears specific for AA in that it is not mimicked by other fatty acids, whether saturated or unsaturated. LDs are formed by two different routes: (i) the direct entry of AA into triacylglycerol and (ii) activation of intracellular signaling, leading to increased triacylglycerol and cholesteryl ester formation utilizing fatty acids coming from the de novo biosynthetic route. Both routes can be dissociated by the arachidonyl-CoA synthetase inhibitor triacsin C, which prevents the former but not the latter. LD formation by AA-induced signaling predominates, accounting for 60-70% of total LD formation, and can be completely inhibited by selective inhibition of the group IVA cytosolic phospholipase A 2α (cPLA 2α), pointing out this enzyme as a key regulator of AA-induced signaling. LD formation in AA-treated monocytes can also be blocked by the combined inhibition of the mitogen-activated protein kinase family members p38 and JNK, which correlates with inhibition of cPLA 2α activation by phosphorylation. Collectively, these results suggest that concomitant activation of p38 and JNK by AA cooperate to activate cPLA 2α, which is in turn required for LD formation possibly by facilitating biogenesis of this organelle, not by regulating neutral lipid synthesis.
Versión del editorhttp://dx.doi.org/10.1194/jlr.M028423
Identificadoresdoi: 10.1194/jlr.M028423
issn: 0022-2275
e-issn: 1539-7262
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