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Orexin A receptor 1(OX1R) activation increases expression of cytokines in PC12 cells
Author(s) -
Alharbi Wafa Fhad,
Bigalke Jeremy,
Chen QingHui,
Shan Zhiyang Jenny
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.692.10
Subject(s) - orexin , junb , orexin receptor , medicine , orexin a , endocrinology , signal transduction , chemistry , microbiology and biotechnology , receptor , biology , transcription factor , neuropeptide , biochemistry , gene
Orexin A is a multifunctional neuropeptide that regulates arousal , wakefulness, appetite and cardiovascular function. Orexin A exists its function through binding with orexin receptor 1 (OX1R) or orexin receptor 2 (OX2R). However, the downstream signal transduction pathway that orexin system mediated is not well determined. In this study, we investigate the hypothesis that binding of orexin A and OX1R results in activation of extracellular signal‐regulated kinase 1 & 2 (ERK1/2) and subsequently increases in inflammatory cytokines. We test this hypothesis using the neuron‐like PC12 cell which artificially expressing human OX1R. Incubation of human orexin A (100 nM) resulted in a time dependent increase in phosphorylated ERK1/2 (P‐ERK1/2) as well as the mRNA levels of Junb, a subunit of transcription factor AP‐1; leukemia inhibitory factor (LIF), and C‐C motif chemokine ligand 2 (CCL2) , in PC12‐OX1R cells. The maximum increase in Junb was observe in 3 hours, while the maximum increase in LIF (18.3‐fold) and CCL2 (12.8 ‐fold ) was observed in 6 hours following orexin A treatment. There was no significant increases in P‐ERK1/2, Junb, CCL2 and LIF was observed in orexin A treated PC12‐OX2R cells or PC12 cells . Pre‐incubation of orexin A (100 nM) with PD98059, a blocker for ERK1/2 phosphorylation, dramatically attenuated the expression of Junb, LIF and CCL2 in PC12‐OX1R cells. Our results suggested that activation of orexin system activity may though activation or ERK1/2 in turn stimulate AP1‐cytokine signaling. Support or Funding Information [Grant support: NIH R15HL129213 (Shan), Michigan Technological University and Portage Health Foundation research Excellence Fund] This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .