OXER1 activation, but not PKA or PKC activation, increases human adrenocortical cell migration

NEUMAN, I.; LEMIÑA, N. A.; CORNEJO MACIEL, F.

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

9 sociedades científicas argentinas

Lipoxygenase-dependent products of arachidonic acid metabolism act through a membrane receptor named OXER1. These compounds are produced in steroidogenic cells and are required for the activation of steroid production. We found that human adrenocortical H295R cells express OXER1 and that, in this cell type, it is involved in the PKA and PKC-dependent stimulation of steroidogenesis. Other authors have postulated that 5-oxo-ETE is a potent activator of human neutrophil migration and prostate cancer profileration. Both effects are mediated by the activation of it´s receptor. Here we examined the effect of PKA, PKC, and OXER1 signal transduction pathways on the migration of H295R cells. The cells were cultured under different conditions and cell migration was evaluated measuring wound healing 24 h after scratch. Results are shown in arbitrary units as mean ± SEM. Treatment with 5-oxo-ETE (500 nM), agonist of OXER1, produced an increase in cell migration (control 14.3 ± 0.7 vs. 5-oxo-ETE 25.3 ± 2.5, P <0.003). This result was also obtained using a cell line characterized by the stable overexpression of OXER1. In addition, H295R cells treated with 1 mM 8Br-cAMP or 0.1 mM angiotensin II did not change the migration rate (control 14.3 ± 0.7; 8Br-cAMP 10.2 ± 1.8; AII 17.5 ± 1.8). Therefore, the activation of PKA and PKC kinases might not be involved in the activation of the migration process. OXER1 activation might promote cell migration through its own signal transduction pathway. Future experiments should focus on signal transduction pathways triggered by OXER1 activation.