PKB/Akt phosphorylation in human umbilical vein endothelial cells is highly induced by myo-inositol and D-chiro inositol: novel potential insights in the pathogenesis of preeclampsia

Immunological alterations, endothelial dysfunction and insulin resistance characterize preeclampsia. The signaling pathways mediating these biological abnormalities converge on PKB/Akt, an intracellular kinase regulating cell survival, proliferation and metabolism. 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 was evaluated in human endothelial cells in vitro . Assessing time-course and dose-response analyses. To assess the potential activation of intracellular signals relevant for cell survival, HUVEC were exposed to increasing doses of MI or DCI, and PKB/Akt phosphorylation on Ser473 was evaluated with a specific antibody. Time-course analysis of PBK/Akt phosphorylation in response to 1 mM MI and 1 mM DCI showed a significant increase that was already evident after 5 min. PKB/Akt phosphorylation induced by MI peaked at 15 min and remained stable thereafter, while incubation with DCI showed a progressive time-related increase. Exposure to increasing concentrations of MI for 5 min induced a dose-dependent increase in PKB/Akt phosphorylation, which was augmented approximately 6-fold with 1 mM MI ( P P p in vitro . It is tempting to speculate that the increased production of DCI-phosphoglycans during preeclampsia may exert the positive effect to activate PKB/Akt and potentially other intracellular proteins involved in cell survival and metabolism.