Orexin-A regulates cell apoptosis in human H295R adrenocortical cells via orexin receptor type 1 through the AKT signaling pathway.

Numerous studies have demonstrated the ability of orexin-A to regulate adrenocortical cells through the mitogen-activated protein kinase signaling pathway. In the present study, human H295R adrenocortical cells were exposed to orexin-A (10(-10)-10(-6) M), with orexin receptor type 1 (OX1 receptor) antagonist SB334867 or AKT antagonist PF-04691502. It was found that orexin-A stimulated H295R cell proliferation, reduced the pro-apoptotic activity of caspase-3 to protect against apoptotic cell death and increased cortisol secretion. Furthermore, phospho-AKT protein was increased by orexin-A. SB334867 (10(-6) M) and PF-04691502 (10(-6) M) abolished the effects of orexin-A (10(-6) M). These results suggested that the orexin-A/OX1 receptor axis has a significant pro-survival function in adrenal cells, which is mediated by AKT activation. Further studies investigating the effects of orexin-A-upregulation may further elucidate the diverse biological effects of orexin-A in adrenal cells.