title: Orexin-A regulates cell apoptosis in human H295R adrenocortical cells via orexin receptor type 1 through the AKT signaling pathway.
abstract: 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.
authors.affiliation: Department of Orthopedic Surgery, First Affiliated Hospital, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Xiaocen
authors.initials: X
authors.lastname: Chang
authors.affiliation: Department of Endocrinology, First Affiliated Hospital, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Yuyan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Orthopedic Surgery, First Affiliated Hospital, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Shujing
authors.initials: S
authors.lastname: Ju
authors.affiliation: Department of Orthopedic Surgery, First Affiliated Hospital, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Guo
mesh_terms: D000302:Adrenal Cortex / Q000166:cytology; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation; D002470:Cell Survival; D015870:Gene Expression; D006801:Humans; D064446:Orexin Receptors / Q000235:genetics / Q000378:metabolism*; D000068797:Orexins / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C578630:HCRTR1 protein, human; D064446:Orexin Receptors; D000068797:Orexins; D051057:Proto-Oncogene Proteins c-akt; C505407:CASP3 protein, human; D053148:Caspase 3