Ultraviolet A Radiation-Induced Immediate Iron Release Is a Key Modulator of the Activation of NF-κB in Human Skin Fibroblasts

Abstract

Ultraviolet A (UVA, 320-400 nm) radiation, an oxidizing component of sunlight, leads to an immediate increase in the labile iron in human skin fibroblasts. Exposure of skin fibroblasts to UVA radiation is also known to induce nuclear factor-kappaB (NF-kappaB) DNA-binding activity, although the underlying mechanism is unclear. We report here that in skin fibroblasts, the extent of NF-kappaB activation by UVA tightly correlates with the level of "UVA-induced" labile iron release as shown by both iron chelation and iron loading treatments. Furthermore, our data indicate that the slow kinetics of induction of NF-kappaB by UVA relative to other oxidants previously studied is due to a transient increase in permeability of nuclear membrane to proteins and occurs as a result of labile iron-mediated damage to nuclear membrane. Since in addition to iron chelators, lipid peroxidation inhibitors also decrease the UVA-mediated induction of NF-kappaB, we propose that the rapid release of labile iron by UVA might act as a catalyst to exacerbate the generation of lipid secondary messengers in skin cell membranes that are responsible for induction of NF-kappaB. This novel role for iron in amplifying NF-kappaB mobilization in response to UVA-induced oxidative stress aids understanding of its involvement in UV-induced skin inflammation.

Topical treatment with pterostilbene, a natural phytoalexin, effectively protects hairless mice against UVB radiation-induced skin damage and carcinogenesis

“…In fact, since it has been shown that exposure of skin cells to e.g. UVA induces an immediate release of labile iron [33], this mechanism could be (at least in part) responsible of the inflammatory and oxidative damages reported here. Therefore the photoprotective effects elicited by polyphenolic phytochemicals could involve, as previously suggested, potential iron chelating effects (see e.g.…”

Nrf2 deficiency causes lipid oxidation, inflammation, and matrix-protease expression in DHA-supplemented and UVA-irradiated skin fibroblasts

“…Firstly, heme oxygenase 1, as the strongest UVA/oxPL regulated gene is essential to restore the cellular heme/iron homeostasis after UVA insult [76,77] and has well established anti-inflammatory properties, including reduction of TNFα synthesis. Glutathione peroxidase and the enzymes necessary for de-novo glutathione synthesis, GCLM and GCLC all contribute to limit UVA induced lipid hydroperoxide generation, which promotes expression of MMP1 (and of its mouse homolog MMP13).…”

A comparative evaluation of coenzyme Q10-loaded liposomes and solid lipid nanoparticles as dermal antioxidant carriers

“…27 Recently, Reelfs et al have shown that labile iron in skin fibroblast, which is involved in the activation of a number of transcription factors, was released by UVA irradiation. 28 It is also known that 1 O 2 can initiate c-jun N-terminal kinase signaling, which leads to interstitial collagenase induction as well as the synthesis of proinflammatory cytokines in UVA-irradiated fibroblasts. 27 It was also proven that aging skin fibroblasts have decreased catalase activity.…”