International journal of molecular medicine, 2014-07, Vol.34 (1), p.153-159
2014
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- Autor(en) / Beteiligte
- Titel
- Orexin A protects cells from apoptosis by regulating FoxO1 and mTORC1 through the OX1R/PI3K/AKT signaling pathway in hepatocytes
- Ist Teil von
- International journal of molecular medicine, 2014-07, Vol.34 (1), p.153-159
- Ort / Verlag
- Greece: D.A. Spandidos
- Erscheinungsjahr
- 2014
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1107-3756eISSN: 1791-244XDOI: 10.3892/ijmm.2014.1769Titel-ID: cdi_proquest_journals_1932350379
- Format
- –
- Schlagworte
- Animals, Apoptosis, Apoptosis - drug effects, Benzoxazoles - pharmacology, Cancer, cell apoptosis, Cell cycle, Cell growth, Culture Media, Serum-Free, Dose-Response Relationship, Drug, Everolimus, forkhead box O1, Forkhead Transcription Factors - antagonists & inhibitors, Forkhead Transcription Factors - genetics, Forkhead Transcription Factors - metabolism, Gene Expression Regulation, Hepatocytes - cytology, Hepatocytes - drug effects, Hepatocytes - metabolism, Intracellular Signaling Peptides and Proteins - genetics, Intracellular Signaling Peptides and Proteins - metabolism, Intracellular Signaling Peptides and Proteins - pharmacology, Kinases, Laboratory animals, Male, mammalian target of rapamycin 1, Mechanistic Target of Rapamycin Complex 1, Multiprotein Complexes - antagonists & inhibitors, Multiprotein Complexes - genetics, Multiprotein Complexes - metabolism, Nerve Tissue Proteins - antagonists & inhibitors, Nerve Tissue Proteins - genetics, Nerve Tissue Proteins - metabolism, Neuropeptides - genetics, Neuropeptides - metabolism, Neuropeptides - pharmacology, orexin A, orexin receptor 1, Orexin Receptor Antagonists, Orexin Receptors - genetics, Orexin Receptors - metabolism, Orexins, Phosphatidylinositol 3-Kinases - antagonists & inhibitors, Phosphatidylinositol 3-Kinases - genetics, Phosphatidylinositol 3-Kinases - metabolism, Phosphorylation, PI3K/AKT, Polyclonal antibodies, Primary Cell Culture, Protein synthesis, Proteins, Proto-Oncogene Proteins c-akt - antagonists & inhibitors, Proto-Oncogene Proteins c-akt - genetics, Proto-Oncogene Proteins c-akt - metabolism, Pyridones - pharmacology, Pyrimidines - pharmacology, Quinolones - pharmacology, Rats, Rats, Sprague-Dawley, Rodents, Signal Transduction - drug effects, Sirolimus - analogs & derivatives, Sirolimus - pharmacology, TOR Serine-Threonine Kinases - antagonists & inhibitors, TOR Serine-Threonine Kinases - genetics, TOR Serine-Threonine Kinases - metabolism, Urea - analogs & derivatives, Urea - pharmacology