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Abstract Oxidative stress induced by medium-wavelength ultraviolet radiation (UVB) is one of the most dangerous environmental stressors for the skin. Therefore, various medicinal remedies aim to prevent the harmful effects of UVB or support the recovery of the damaged cells. This study aimed to evaluate the impact of bioactive phytocannabinoid cannabigerol (CBG) together with 3-O-ethyl ascorbic acid (EAA), a stable, lipophilic derivative of the antioxidant vitamin C, on UVB-induced changes of proteome in cultured human keratinocytes 24 h after treatment. Surprisingly, proteomic analysis revealed very prominent CBG and EAA effects on kinases. These changes mainly influenced ERK1/2, IKK, MAP3K7, MAPK14, RIPK2, and NLK. Their expression was decreased by CBG and EAA, especially if used together after UVB-irradiation, so the effects of UVB were abolished restoring the profile of kinases to non-irradiated control. Moreover, CBG and EAA also reduced the UVB-induced modifications of proteins by the lipid peroxidation product 4-hydroxynonenal, especially in the case of AKT, Camkk1, cJun, ERK1, IKKα, MAPK11 and PERK. We conclude that, by maintaining proteome stability and kinase-dependent signalling, both CBG and EAA may support the recovery of human keratinocytes exposed to UVB radiation, especially if applied together, while the time-dependence of these effects should be further studied.

Melanoma is one of the most malignant forms of skin cancer, characterised by the highest mortality rate among affected patients. This study aims to analyse and compare the effects of lipid extracts from the microalgae Nannochloropsis oceanica (N.o.) and Chlorococcum amblystomatis (C.a.) on the intra and extracellular proteome of UVA-irradiated melanoma cells using a three-dimensional model. Proteomic analysis revealed that UVA radiation significantly increases the levels of pro-inflammatory proteins in melanoma cells. Treatment with algae extracts reduced these protein levels in both non-irradiated and irradiated cells. Furthermore, untreated cells released proteins responsible for cell growth and proliferation into the medium, a process hindered by UVA radiation through the promotion of pro-inflammatory molecules secretion. The treatment with algae extracts effectively mitigated UVA-induced alterations. Notably, UVA radiation significantly induced the formation of 4-HNE and 15-PGJ2 protein adducts in both cells and the medium, while treatment with algae extracts stimulated the formation of 4-HNE-protein adducts and reduced the level of 15-PGJ2-protein adducts. However, both algae extracts successfully prevented these UVA-induced modifications. In conclusion, lipid extracts from N.o. and C.a. appear to be promising agents in supporting anti-melanoma therapy. However, their potent protective capacity may limit their applicability, particularly following cells exposure to UVA. [ABSTRACT FROM AUTHOR]

Oxidative stress induced by medium-wavelength ultraviolet radiation (UVB) is one of the most dangerous environmental stressors for the skin. Therefore, various medicinal remedies aim to prevent the harmful effects of UVB or support the recovery of the damaged cells. This study aimed to evaluate the impact of bioactive phytocannabinoid cannabigerol (CBG) together with 3-O-ethyl ascorbic acid (EAA), a stable, lipophilic derivative of the antioxidant vitamin C, on UVB-induced changes of proteome in cultured human keratinocytes 24 h after treatment. Surprisingly, proteomic analysis revealed very prominent CBG and EAA effects on kinases. These changes mainly influenced ERK1/2, IKK, MAP3K7, MAPK14, RIPK2, and NLK. Their expression was decreased by CBG and EAA, especially if used together after UVB-irradiation, so the effects of UVB were abolished restoring the profile of kinases to non-irradiated control. Moreover, CBG and EAA also reduced the UVB-induced modifications of proteins by the lipid peroxidation product 4-hydroxynonenal, especially in the case of AKT, Camkk1, cJun, ERK1, IKKα, MAPK11 and PERK. We conclude that, by maintaining proteome stability and kinase-dependent signalling, both CBG and EAA may support the recovery of human keratinocytes exposed to UVB radiation, especially if applied together, while the time-dependence of these effects should be further studied. [ABSTRACT FROM AUTHOR]

Previous studies in MRL+/+ mice suggest involvement of oxidative stress (OS) in trichloroethene (TCE)-mediated autoimmunity. However, molecular mechanisms underlying the autoimmunity remain to be fully elucidated. Even though toll-like receptors (TLRs) and Nuclear factor (erythroid-derived 2)-like2 (Nrf2) pathways are implicated in autoimmune diseases (ADs), interplay of OS, TLR and Nrf2 in TCE-mediated autoimmune response remains unexplored. This study was, therefore, undertaken to clearly establish a link among OS, TLR4 and Nrf2 pathways in TCE-induced autoimmunity. Groups of female MRL+/+ mice were treated with TCE, sulforaphane (SFN, an antioxidant) or TCE + SFN (TCE, 10 mmol/kg, i.p. , every 4th day; SFN, 8 mg/kg, i.p. , every other day) for 6 weeks. TCE exposure led to greater formation of serum 4-hydroxynonenal (HNE)-protein adducts, HNE-specific circulating immune complexes (CICs) and protein carbonyls which were associated with significant increases in serum antinuclear antibodies (ANAs). Moreover, incubation of splenocytes from TCE-treated mice with HNE-modified proteins resulted in enhanced splenocyte proliferation and cytokine release evidenced by increased expression of cyclin D3, Cyclin-dependent kinase 6 (CDK6) and phospho-pRb as well as increased release of IL-6, TNF-α and INF-γ. More importantly, TCE exposure resulted in increased expression of TLR4, MyD88, IRAK4, NF-kB and reduced expression of Nrf2 and HO-1 in the spleen. Remarkably, SFN supplementation not only attenuated TCE-induced OS, upregulation in TLR4 and NF-kB signaling and downregulation of Nrf2, but also ANA levels. These results, in addition to providing further support to a role of OS, also suggest that an interplay among OS, TLR4 and Nrf2 pathways contributes to TCE-mediated autoimmune response. Attenuation of TCE-mediated autoimmunity by SFN provides an avenue for preventive and/or therapeutic strategies for ADs involving OS. Unlabelled Image • TCE exposure causes dysregulation of TLR4 signaling and impairment of Nrf2 pathway • HNE-protein adducts play a vital role in TCE-mediated inflammation/autoimmunity • SFN supplementation ameliorates TCE-mediated oxidative stress and autoimmunity • Interplay of oxidative stress, TLR4 and Nrf2 pathways contributes to autoimmunity [ABSTRACT FROM AUTHOR]