PKB/Akt and MAPK/ERK phosphorylation is highly induced by inositols: Novel potential insights in endothelial dysfunction in preeclampsia.

PKB/Akt and MAP/ERK are intracellular kinases regulating cell survival, proliferation and metabolism and as such hold a strategical role in preeclampsia. In fact intracellular pathways related to immunological alterations, endothelial dysfunction and insulin resistance in preeclampsia converge on these molecules. Inositol second messengers are involved in metabolic and cell signaling pathways and are highly expressed during preeclampsia. To evaluate the pathophysiological significance of this response, the effect of myo-inositol and d-chiro inositol on the activation of PKB/Akt and MAPK/ERK was assessed in human endothelial cells in vitro. Time-course and dose-response analyses of phosphorylation following incubation with inositols showed an approximately 6-fold and 15-fold increase for myo-inositol and d-chiro inositol (p<0.05), respectively. Both inositols promoted a significantly higher PKB/Akt and MAPK/ERK phosphorylation than insulin. Thus, exogenously administered inositols can activate PKB/Akt and MAPK/ERK in human endothelial cells in vitro. The increased production of d-chiro inositol phosphoglycans (IPG-P) during preeclampsia may thus represent a compensatory response, potentially promoting cell survival and metabolism.