UVA, UVB and UVC Induce Differential Response Signaling Pathways Converged on the eIF2α Phosphorylation

Abstract

It is clear that solar UV irradiation is a crucial environmental factor resulting in skin diseases partially through activation of cell signaling toward altered gene expression and reprogrammed protein translation. Such a key translational control mechanism is executed by the eukaryotic initiation factor 2α subunit (eIF2α) and the downstream events provoked by phosphorylation of eIF2α at Ser(51) are clearly understood, but the upstream signaling mechanisms on the eIF2α-Ser(51) phosphorylation responses to different types of UV irradiations, namely UVA, UVB and UVC, are still not well elucidated. Herein, our evidence reveals that UVA, UVB and UVC all induce a dose- and time-dependent phosphorylation of eIF2α-Ser(51) through distinct signaling mechanisms. UVA-induced eIF2α phosphorylation occurs through MAPKs, including ERKs, JNKs and p38 kinase, and phosphatidylinositol (PI)-3 kinase. By contrast, UVB-induced eIF2α phosphorylation is through JNKs and p38 kinase, but not ERKs or PI-3 kinase, whereas UVC-stimulated response to eIF2α phosphorylation is via JNKs alone. Furthermore, we have revealed that ATM is involved in induction of the intracellular responses to UVA and UVB, rather than UVC. These findings demonstrate that wavelength-specific UV irradiations activate differential response signaling pathways converged on the eIF2α phosphorylation. Importantly, we also show evidence that a direct eIF2α kinase PKR is activated though phosphorylation by either RSK1 or MSK1, two downstream kinases of MAPKs/PI-3 kinase-mediated signaling pathways.

Low Dose Ultraviolet B Irradiation Increases Hyaluronan Synthesis in Epidermal Keratinocytes via Sequential Induction of Hyaluronan Synthases Has1–3 Mediated by p38 and Ca2+/Calmodulin-dependent Protein Kinase II (CaMKII) Signaling*

“…Both up-regulation (24 -28) and down-regulation (29 -31) have been reported. The response undoubtedly depends on the cellular background, radiation type (narrowband versus broadband) and wavelength, dosage, exposure scheme (single, repeated, or chronic), and the time point of observation (32)(33)(34). Release of KGF and IL-1␤ has been implicated in the hyaluronan response seen in UV-treated keratinocyte cultures (25).…”

Ultraviolet Radiation in Wound Care: Sterilization and Stimulation

“…48 In the same study, it has also been revealed that AT-mutated (ATM) kinase, which is also located at or near the beginning of multiple signaling pathways is involved in induction of the intracellular responses to UVA and UVB, rather than UVC. 48 Further, ROS generated by UV irradiation was shown to be critical for signal transduction cascades such as MAPK (p38, ERK, and JNK). 21,49 p38 is an important inducer of cell cycle arrest and UVinduced double-strand breaks have also been shown to activate p38 through the DNA damage sensors ATM and Rad3-related protein kinase (ATR).…”

“…47 It executes a key translational control mechanism following UV irradiation. 48 UVA, UVB, and UVC all induce a dose-and time-dependent phosphorylation of eIF2a-Ser51 through distinct signaling mechanisms. 48 It was shown in a recent study that, while UVAinduced eIF2a phosphorylation occurs through mitogen-activated protein kinases (MAPKs), including ERK, c-Jun N-terminal kinase ( JNK) and p38 kinase, and phosphatidylinositol (PI)-3 kinase, UVBinduced eIF2a phosphorylation through JNKs and p38 kinase, but not ERKs or PI-3 kinase, whereas UVC-stimulated response to eIF2a phosphorylation is via JNKs alone.…”

“…48 UVA, UVB, and UVC all induce a dose-and time-dependent phosphorylation of eIF2a-Ser51 through distinct signaling mechanisms. 48 It was shown in a recent study that, while UVAinduced eIF2a phosphorylation occurs through mitogen-activated protein kinases (MAPKs), including ERK, c-Jun N-terminal kinase ( JNK) and p38 kinase, and phosphatidylinositol (PI)-3 kinase, UVBinduced eIF2a phosphorylation through JNKs and p38 kinase, but not ERKs or PI-3 kinase, whereas UVC-stimulated response to eIF2a phosphorylation is via JNKs alone. 48 In the same study, it has also been revealed that AT-mutated (ATM) kinase, which is also located at or near the beginning of multiple signaling pathways is involved in induction of the intracellular responses to UVA and UVB, rather than UVC.…”

UVA-induced protection of skin through the induction of heme oxygenase-1

“…UV light that reaches the earth is divided into ultraviolet A (UVA, 320-400 nm) and ultraviolet B (UVB, 290-320 nm), and the UVA waveband can be further divided into UVA1 (340-400 nm) and UVA2 (320-340 nm) (2,3). UVB constitutes less than 10% of solar UV, and it is generally thought to be the most deleterious radiation of sunlight and the major wavelength involved in erythema, immunosuppression and carcinogenesis outcomes (4).…”