Mechanism for dynamic regulation of iNOS expression after UVB-irradiation
Article first published online: 16 MAR 2012
Copyright © 2012 Wiley Periodicals, Inc.
Volume 52, Issue 8, pages 627–633, August 2013
How to Cite
Lu, W. and Wu, S. (2013), Mechanism for dynamic regulation of iNOS expression after UVB-irradiation. Mol. Carcinog., 52: 627–633. doi: 10.1002/mc.21898
- Issue published online: 12 JUL 2013
- Article first published online: 16 MAR 2012
- Manuscript Accepted: 14 FEB 2012
- Manuscript Revised: 6 FEB 2012
- Manuscript Received: 6 JAN 2012
- ultraviolet B (UVB);
- eukaryotic initiation factor 2 (eIF2);
- nitric oxide synthase (NOS);
- translational regulation
Ultraviolet B (UVB) induces an immediate activation of cNOSs, which contributes to the early release of nitric oxide after irradiation. UVB also induces the expression of iNOS, which peaks at both the mRNA and protein level near 24 h post-irradiation. The induced expression of iNOS contributes largely to the late elevation of nitric oxide after UVB irradiation. However, the regulation of iNOS expression in the early stages of UVB irradiation is not well studied. We previously reported that the UVB-induced early release of nitric oxide leads to the activation of PERK and GCN2, which phosphorylate the alpha-subunit of eIF2 and inhibit protein synthesis. In this report, we demonstrate that eIF2 phosphorylation plays a critical role in regulation of iNOS expression in the early-phase (with in 12 h) of UVB irradiation. Our data shows that with an increased phosphorylation of eIF2, the iNOS protein expression was reduced even though the iNOS mRNA expression was linearly increased in HaCaT and MEF cells after UVB irradiation. The UVB-induced dynamic up- and down-regulation of iNOS expression was almost completely lost in MEFA/A cells, which contain a nonphosphorylatable S51A mutation on eIF2. Our results suggest that the UVB-induced eIF2 phosphorylation does not only regulate iNOS expression at the translational level, but at the transcriptional level as well. © 2012 Wiley Periodicals, Inc.