PAC1-R is neuropeptide PACAP (pituitary adenylate cyclase activating polypeptide) preferring receptor mediates the antioxidant and cytoprotective effects of PACAP. It was found in this research that in both PAC1R-CHO cells with high expression of PAC1R-eGFP and retinal ganglion cells (RGC-5) with natural expression of PAC1-R, blue light and hydrogen peroxide (H2O2) trigger the significant nuclear translocation of PAC1-R, and the nuclear translocation of PAC1-R was positive correlation with the up-regulation of expression level and promoter activity of PAC1-R its own, while red light worked much less efficiently than blue light. Reactive oxygen species (ROS) scavenger NAC (N-acetyl-L-cysteine) and palmitoylation inhibitor 2-bromopalmitate (2-BP) disturbed the nuclear shifting associated with the correlative up-regulation of PAC1 significantly, and PAC1-R mutant (M-PAC1-R) on Cys25/Ala25 displayed the significant decreased nuclear trafficking efficiency. Furthermore, the Western Blot results with the antibody raised against the C-terminal of PAC1-R showing PAC1-R in the nucleus was fragmentation hinting that C-terminal of PAC1-R with theoretical nuclear location signal (NLS) may be involved in activation of PAC1-R promoter in the nucleus. All above results indicated that PAC1-R makes the nuclear translocation to trigger the activation of PAC1-R itself promoter resulting into the up-regulation of of PAC1-R in response to the oxidative stress induced by blue light and ROS such as H2O2 .
Keywords: Blue light; Nuclear translocation; Pituitary adenylate cyclase-activating polypeptide receptor 1; Promoter; Reactive oxygen species.
Copyright © 2021 Elsevier B.V. All rights reserved.