Orexin A protects cells from apoptosis by regulating FoxO1 and mTORC1 through the OX1R/PI3K/AKT signaling pathway in hepatocytes

  • Authors:
    • Shu-Jing Ju
    • Yuyan Zhao
    • Xiaocen Chang
    • Lei Guo
  • View Affiliations

  • Published online on: May 5, 2014     https://doi.org/10.3892/ijmm.2014.1769
  • Pages: 153-159
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Abstract

Orexin A and B are multifunctional neuropeptides that are involved in the regulation of food intake, energy metabolism, glucose regulation and wakefulness. They signal through two G-protein‑coupled receptors (GPCR): orexin receptor 1 (OX1R) and orexin receptor 2 (OX2R). Previous studies have shown that orexins interact with PI3K/AKT signaling pathways through OX1R-coupling in other cell types, but are seldom involved in hepatocytes. In the present study, reverse transcription (RT)-PCR and western blot analysis revealed that OX1R mRNA expression and activation in rat hepatocytes in vitro were upregulated by exogenous orexin A (10-10 to 10-6 M) in a dose-dependent manner. The result showed that orexin A affects increasing cell proliferation and protects cells from apoptosis. Additionally, inhibition studies showed that orexin A induced forkhead box O1 (FoxO1) and mammalian target of rapamycin 1 (mTORC1) phosphorylation, while OX1R antagonist (SB334867, 10-6 M), AKT antagonist (PF-04691502, 10-6 M), Foxo1 inhibitor (AS1842856, 10-6 M) or mTORC1 inhibitor (everolimus, 10-5 M) blocked these effects of orexin A. The results of the present study showed a possible effect of orexin A on cell apoptosis in regulating Foxo1 and mTORC1 through the OX1R/PI3K/AKT signaling pathway in rat hepatocytes.

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July 2014
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APA
Ju, S., Zhao, Y., Chang, X., & Guo, L. (2014). Orexin A protects cells from apoptosis by regulating FoxO1 and mTORC1 through the OX1R/PI3K/AKT signaling pathway in hepatocytes. International Journal of Molecular Medicine, 34, 153-159. https://doi.org/10.3892/ijmm.2014.1769
MLA
Ju, S., Zhao, Y., Chang, X., Guo, L."Orexin A protects cells from apoptosis by regulating FoxO1 and mTORC1 through the OX1R/PI3K/AKT signaling pathway in hepatocytes". International Journal of Molecular Medicine 34.1 (2014): 153-159.
Chicago
Ju, S., Zhao, Y., Chang, X., Guo, L."Orexin A protects cells from apoptosis by regulating FoxO1 and mTORC1 through the OX1R/PI3K/AKT signaling pathway in hepatocytes". International Journal of Molecular Medicine 34, no. 1 (2014): 153-159. https://doi.org/10.3892/ijmm.2014.1769