Angiotensin II promotes activation of mTOR pathway components in H295R adrenocortical cells

KATIA E. HELFENBERGER; ANA FERNANDA CASTILLO; ANA FIORE; PAOLA FINOCCHIETTO; ERNESTO J. PODESTÁ; CECILIA PODEROSO

Mar del Plata

Congreso; LXI Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2016

SAIC

Primary aldosteronism (PA) is one of the most common causesof endocrine hypertension, accounting for 5 to 10% of hypertensivepatients. It is characterized by autonomous excessive aldosteronesecretion by the adrenal gland. In particular, studies have focusedon the PI3K/AKT/mTOR pathway, which has been described tobe overactive in adrenal carcinoma and other tumor types. Whilethe activation and participation of this pathway in hypersecretionof aldosterone by zona glomerulosa has been described, a possiblehormonal regulation of this pathway is not known in adrenalgland up to date. It has been described that the enzyme ACSL4(acyl-CoA synthetase 4) modulates mTOR pathway, promotingphosphorylation of its components (AKT, p70 kinase, S6 ribosomalprotein, mTOR complex) in breast cancer cells. ACSL4 is alsoinvolved in physiological steroid production, including aldosteronesynthesis. Then, the aim of this work is to study the mechanisms involved in the modulation of the mTOR pathway in human adrenocorticalcells and a possible role of ACSL4 in this process. Weused human adrenocarcinoma H295R cells described as a modelof PA, capable to respond to Angiotensin II (Ang II) stimulation. Weobserved by immunoblot that Ang II promotes AKT phosphorylation(pAKT) in serine 308, which occurs upstream mTOR complexactivation, in a time-dependent manner (two-fold increase after AngII 1h). Ang II stimulation elicits a significant increase of phospho-S6(Ang II 30 min: 1.4 **p