Premium
Orexin A receptor 1 (OX1R) activation increases CamK2 expression in PC12 cells
Author(s) -
Fan Yuanyuan,
Jiang Enshe,
Chen Qinchui,
Shan Zhiying
Publication year - 2017
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.31.1_supplement.lb802
Subject(s) - orexin , orexin a , medicine , calcium , endocrinology , calcium in biology , receptor , orexin receptor , intracellular , microbiology and biotechnology , chemistry , biology , neuropeptide
Previous study have demonstrated that orexin receptor activation resulted in an increase in sympathetic activity and elevation in intracellular calcium levels. This observation coupled with the important role of calcium on the control of Ca2+/calmodulin‐dependent protein kinase II (CamK2) activity have led us to hypothesize that orexin system may involve in increasing sympathetic nerve activity through stimulating the expression of CamK2. In this study, we test this hypothesis using the neuron‐like PC12 cell which artificially expressing human orexin A receptor 1 (OX1R). Consistent with previous finding, incubation of human orexin A (100 nM) dramatically increased the cytosolic calcium level measured with a fluorescent calcium probe (Fluo‐4AM) in PC12‐OX1R cells. In addition, orexin A treatment (100nM) for 6 hours resulted in significant increases in the mRNA levels of calcium dependent protein early growth response 1 (EGR1, 25‐fold, P<0.05), CamK2a (2‐fold, P<0.05), CamK2b (4‐fold, P<0.05) as well as Fosl1 (9‐fold, P<0.05), a chronic neuronal activation marker, compared to control group. These data suggest that binding of orexin A and OX1R increases calcium influx which may subsequently stimulates EGR1 expression, the EGR1, as a major transcription regulator, may modulate expression of many genes including the expression of CamK2, which eventually increase neural firing. Our further study will investigate whether or not blockage of CamK2 will attenuate the increase in sympathetic nerve activity. Support or Funding Information NIH R15HL129213 (Shan)