ACYL-COA SYNTHETASE 4 INHIBITION DECREASES ADRENOCORTICAL HUMAN CELL PROLIFERATION SUSTAINED BY ANGIOTENSIN II

HELFENBERGER, KATIA E.; FIORE, ANA Z.; HERRERA, LUCÍA ; BENZO, YANINA ; MALOBERTI, PAULA M.; PODEROSO, CECILIA

CABA

Congreso; Reunión conjunta de sociedades de Biociencias, 2017; 2017

Angiotensin II (Ang II) is one of the most important stimuli of adrenal glomerulosa cells. Ang II stimulates proliferation of adrenocortical cells in vivo and primary bovine glomerulosa cells in vitro, although rat glomerulosa cells in vitro exhibit hypertrophy rather than proliferation by Ang II. Then, proliferating effects of Ang II rely on multiple factors. In adrenal cells, proliferation depends on the activation of the PI3K/Akt/mTOR pathway, which is overactive in adrenocortical tumor and others. The enzyme acyl-CoA synthetase 4 (ACSL4) activates mTOR, promoting phosphorylation of its components and inducing proliferation in breast cancer cells. ACSL4 is highly expressed in adrenal gland regulated by Ang II and involved in aldosterone synthesis, in H295R adrenocortical human cells. The aim of this work is to study a possible role of ACSL4 in Ang II-modulation of mTOR pathway and proliferation in human adrenocortical cells. We used H295R human adrenocortical cell line that responds to Ang II stimulation. We observed by immunoblot that Ang II promotes a time-dependent phosphorylation of Ribosomal protein S6 (RpS6), activated downstream mTOR pathway. RpS6 phosphorylation is significantly decreased when cells were treated with Triacsin C (T), a potent ACSL4 inhibitor (Ang II vs. Ang II + T; 4h: 4.71 vs. 0.66; 6h: 5.41 vs. 1.05 ***p