Mechanism for dynamic regulation of iNOS expression after UVB‐irradiation

Abstract

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 MEF(A/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.

Fernblock (Polypodium leucotomos Extract): Molecular Mechanisms and Pleiotropic Effects in Light-Related Skin Conditions, Photoaging and Skin Cancers, a Review

“…Other pro-inflammatory mechanisms of UV radiation include ROS-induced peroxidation, which damages cellular membranes and induces activation of different isoforms of nitric oxide synthase (iNOS). UV-induction of iNOS seems to mediate VEGF-induced angiogenesis and hyperpermeability [ 36 ].…”

Polypeptide from Chlamys farreri suppresses ultraviolet-B irradiation-induced apoptosis through restoring ER redox homeostasis, scavenging ROS generation, and suppressing the PERK-eIF2a-CHOP pathway in HaCaT cells

“…Farrukh et al have declared that UVB irradiation induces ER stress and PERK-eIF2a pathway only in Hs68 fibroblasts but not in HaCaT cells [8]. However, the studies from Lu et al was in contrast with these findings and showed that eIF2a, the downstream factor of PERK, could be phosphorylated by UVB irradiation in HaCaT cells [23,24]. Therefore, further in-depth studies are still needed to clarify the association between UVB irradiation and ER stress-induced PERK-eIF2a pathway activation in the HaCaT cells.…”

Caffeic Acid Inhibits UVB‐induced Inflammation and Photocarcinogenesis Through Activation of Peroxisome Proliferator‐activated Receptor‐γ in Mouse Skin

“…Besides, MAPKinases the involvement of VEGF, TGF‐ β 1 and iNOS in the skin significantly contributes UVB‐induced photocarcinogenesis. It has been proved that UVB‐induced iNOS mediates VEGF‐induced angiogenesis and hyperpermeability . TGF‐ β 1 overexpression at later stages of carcinogenesis promotes tumor progression, metastasis and epithelial‐to‐mesenchymal transition (EMT), potentially via loss of adhesion molecules, angiogenesis, proteinase activation and immune suppression .…”