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Simultaneous activaction of p38 and JNK by arachidonic acid stimulates the cytosolic phospholipase A2-dependent synthesis of lipid droplets in human monocytes

AuthorsGuijas, Carlos ; Pérez-Chacón, Gema ; Astudillo, Alma M. ; Gil-de-Gómez, Luis ; Rubio, Julio M. ; Balboa, María A. ; Balsinde, Jesús
Issue Date2012
Citation4th European Workshop on Lipid Mediators (2012)
AbstractExposure 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. LD are formed by two different routes, namely (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 by 60-70% of total LD formation, and can be completely inhibited by selective inhibition of the group IVA cytosolic phospholipase A2alpha (cPLA2alpha), pointing out to 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 cPLA2alpha activation by phosphorylation. Collectively, these results suggest that concomitant activation of both p38 and JNK by AA cooperate to activate cPLA2alpha, which is in turn required for LD formation possibly by facilitating biogenesis of this organelle, not by regulating neutral lipid synthesis.
DescriptionResumen del trabajo presentado al Fourth European Workshop on Lipid Mediators (Young session) celebrado en Paris (Francia) del 27 al 28 de septiembre de 2012.
Appears in Collections:(IBGM) Comunicaciones congresos
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