Carlos Alberto de Carvalho Fraga
Posters: J Diabetes Metab
In this study, we investigated the involvement of the Ang-(1-7)/Mas axis in cell migration under hypoxic condition induced by cobaltous chloride and the underlying mechanism. Methods and Results: We first confirmed that Ang-(1-7) decreases HIF-1α signaling in a newly developed hydroxypropyl-β- cyclodextrin (HPBCD)-based Ang-(1-7) nano-formulation in a novel transgenic rat model of inducible insulin resistance and DM2. The chronic administration of this compound prevented the marked elevation of HIF-1α in diabetic rat kidney. Next, mouse embryonic fibroblasts (MEFs) and SCC-9 cells were incubated in a well humidified incubator with 5% CO2 and 95% air at 37 ?C (normoxic condictions). For hypoxic cultures, cells were incubated 150 μM CoCl2 for 24 hours and maintained in a 5% CO2 atmosphere at 37˚C. Then, we divided cells into 4 groups including control, CoCl2, Ang-(1-7) and CoCl2 + Ang-(1-7). HIF-1α protein expression and AKT phosphorylation were decreased in hypoxic cells after treatment with Ang-(1-7). Besides, Ang-(1-7) decreased SCC-9 cell migration in hypoxic condition. Conclusions: In conclusion, our current findings suggest that Ang-(1?7) attenuates HIF-1 α protein stabilization via AKT and Mas receptor-dependent mechanism. In addition, we found that the Ang-(1?7)/Mas receptor inhibit oral cancer cell migration.
