The cross-talk between electrophiles, antioxidant defence and the endocannabinoid system in fibroblasts and keratinocytes after UVA and UVB irradiation

Gęgotek, Agnieszka; Biernacki, Michał; Ambrożewicz, Ewa; Surażyński, Arkadiusz; Wroński, Adam

doi:10.1016/j.jdermsci.2015.11.005

Cited by 64 publications

(72 citation statements)

References 62 publications

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“…The consequences of skin exposure to UV radiation or chemicals are well recognized as a perturbation in the immune system and redox balance resulting in skin aging, as well as the promotion of serious diseases, such as skin cancers [45]. Fibroblasts exposed to highly energetic and strongly cytotoxic and mutagenic UVB irradiation, as well as to less energetic but more penetrating UVA radiation react in different ways to both types of radiation [46, 47]. Hydrogen peroxide, which belongs to ROS, causes various dose-dependent responses in fibroblasts [48].…”

Section: Discussionmentioning

confidence: 99%

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Comparison of protective effect of ascorbic acid on redox and endocannabinoid systems interactions in in vitro cultured human skin fibroblasts exposed to UV radiation and hydrogen peroxide

et al. 2017

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The mechanisms of biological activity of commonly used natural compounds are constantly examined. Therefore, the aim of this study was to compare ascorbic acid efficacy in counteracting the consequences of UV and hydrogen peroxide treatment on lipid mediators and their regulative action on antioxidant abilities. Skin fibroblasts exposed to UVA and UVB irradiation, treated with hydrogen peroxide and ascorbic acid. The redox system was estimated through reactive oxygen species (ROS) generation (electron spin resonance spectrometer) and antioxidants level/activity (HPLC/spectrometry) which activity was evaluated by the level of phospholipid metabolites: 4-hydroxynonenal, malondialdehyde, 8-isoprostanes and endocannabinoids (GC/LC-MS) in the human skin fibroblasts. Protein and DNA oxidative modifications were also determined (LC). The expression of nuclear factor erythroid 2-related factor 2 (Nrf2), its activators and inhibitors as well as pro/anti-apoptotic proteins and endocannabinoid receptors was examined (Western blot) and collagen metabolism was evaluated by collagen biosynthesis and prolidase activity (spectrometry). UVA and UVB irradiation and hydrogen peroxide treatment enhanced activity of xanthine and NADPH oxidases resulting in ROS generation as well as diminution of antioxidant phospholipid protection (glutathione peroxidase-glutathione-vitamin E), what led to increased lipid peroxidation and decreased endocannabinoids level. Dysregulation of cannabinoid receptors expression and environment of transcription factor Nrf2 caused apoptosis induction. Ascorbic acid partially prevented ROS generation, antioxidant capacity diminution and endocannabinoid systems disturbances but only slightly protected macromolecules such as phospholipid, protein and DNA against oxidative modifications. However, ascorbic acid significantly prevented decrease in collagen type I biosynthesis. Ascorbic acid in similar degree prevents UV (UVA and UVB) and hydrogen peroxide-dependent redox imbalance. However, this antioxidant cannot efficiently protect cellular macromolecules and avert metabolic dysregulation leading to apoptosis.

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Section: Discussionmentioning

confidence: 99%

“…Hydrogen peroxide, which belongs to ROS, causes various dose-dependent responses in fibroblasts [48]. However, both above physical and chemical factors develop oxidative stress in the cells [46, 49]. …”

Section: Discussionmentioning

confidence: 99%

Comparison of protective effect of ascorbic acid on redox and endocannabinoid systems interactions in in vitro cultured human skin fibroblasts exposed to UV radiation and hydrogen peroxide

et al. 2017

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“…Quantitation was achieved using an internal standard method (nonadecanoic acid (19:0) and 1,2-dinonadecanoyl- sn -glycero-3-phosphocholine (19:0 PC) were used as internal standards). Details of analysis were described previously [8]. The phospholipid and free fatty acid concentrations were expressed as a microgram per milligram protein.…”

Section: Methodsologymentioning

confidence: 99%

“…The former are generated from hydrogen peroxide during cellular oxygen metabolism via the Fenton and Haber–Weiss reactions in the presence of free iron or copper ions and as a result of high-energy irradiation [6]. Moreover, UV radiation that enhances the activity of NADPH and xanthine oxidases in keratinocytes and fibroblasts leads to the generation of a superoxide anion that, in its protonated form (a hydroperoxyl radical), is a sufficiently strong oxidant that can initiate the oxidation of PUFAs and transform hydrogen peroxide to a hydroxyl radical [7], [8]. As a result, ROS-dependent peroxidation leads to the formation of metabolically active products of lipid cyclization and fragmentation, which is enhanced in fibroblasts and keratinocytes 24 h after UVA and UVB irradiation [8].…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, UV radiation that enhances the activity of NADPH and xanthine oxidases in keratinocytes and fibroblasts leads to the generation of a superoxide anion that, in its protonated form (a hydroperoxyl radical), is a sufficiently strong oxidant that can initiate the oxidation of PUFAs and transform hydrogen peroxide to a hydroxyl radical [7], [8]. As a result, ROS-dependent peroxidation leads to the formation of metabolically active products of lipid cyclization and fragmentation, which is enhanced in fibroblasts and keratinocytes 24 h after UVA and UVB irradiation [8]. The lipid peroxidation products are longer-lived than ROS and initiate chain reactions that further enhance oxidative damage; this is believed to be responsible for the development of skin cancer due to DNA damage [9].…”

Section: Introductionmentioning

confidence: 99%

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Time-dependent effect of rutin on skin fibroblasts membrane disruption following UV radiation

et al. 2017

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Chronic exposure of the skin to solar UV radiation induces a number of biological alterations, including a redox imbalance; therefore, there is an urgent need for skin cells protective compounds. The aim of this study was to determine the effects of natural, previously extensively examined, polyphenol with antioxidant properties – rutin, on UV-induced skin fibroblasts membrane disruption. Accordingly, fibroblasts exposed to UVA and UVB irradiation were incubated with rutin (12 h before and/or up to 24 h after irradiation), and the structural and metabolic changes were examined. Rutin penetration through the fibroblast phospholipid bilayer was aided by UVA-induced bilitranslocase activity 2–4 h after irradiation, while UVB irradiation led to enhanced phospholipid peroxidation and higher membrane permeability to facilitate the interaction of rutin with phospholipids. Lipidomic analysis revealed that 4 h of rutin treatment also partially prevented UVA/B-induced increase in phosphatidylethanolamine and phosphatidylcholine level, as well as their membrane localization, which resulted in an enhanced zeta potential in the cells and liposomes. Moreover, rutin 2 h following irradiation, in a various degree, prevented the increased in phospholipase A2 activity and ROS generation, and partially protected against the reduction of arachidonic and linoleic acids level and the lipid peroxidation product 4-hydroxynonenal level increase. Rutin effectively prevented against decrease in glutathione peroxidase, glutathione and vitamins E and C activities/levels, particularly 2 h following UVA irradiation.In conclusion, highest skin fibroblasts membrane level of rutin occurred in 2–4 h following UVA/B-radiation results in its strongest effect on biomembrane structure and functions and cellular antioxidant system irrespective of the radiation type.

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Rutin and ascorbic acid cooperation in antioxidant and antiapoptotic effect on human skin keratinocytes and fibroblasts exposed to UVA and UVB radiation

et al. 2019

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The combination of ascorbic acid and rutin is frequently used in oral preparations. However, despite numerous protective effects of each component individually, their combined effect on ultraviolet (UV)-irradiated skin cells has never been evaluated. The aim of this study was to evaluate the combined effect of ascorbic acid and rutin on human keratinocytes and fibroblasts exposed to UVA and UVB radiation. Skin keratinocytes and fibroblasts exposed to UVA and UVB radiation were treated with ascorbic acid or/and rutin. The total antioxidant properties of both components, as well as their effect on cellular pro-and antioxidant status, lipid and protein oxidation, transmembrane transport, and pro-inflammatory and pro/ antiapoptotic protein expression were measured. The combination of ascorbic acid and rutin had higher antioxidant properties compared to the activity of the single compound alone, and showed a stronger effect against UV-induced reactive oxygen species generation. The ascorbic acid and rutin combination also showed increased antioxidant enzyme activity (catalase, superoxide dismutase, thioredoxin reductase), which was impaired following UV irradiation. Moreover, ascorbic acid additional stimulated UV-induced bilitranslocase activity responsible for rutin transport, and therefore favored rutin effect on Nrf2 pathway, simultaneously differentiating the reaction of keratinocytes and fibroblasts. In keratinocytes, Nrf2 is strongly activated, while in fibroblasts decreased Nrf2 activity was observed. Used mixture, also significantly silenced UV-induced expression of pro-inflammatory factor NFκB and pro-apoptotic proteins such as caspases 3, 8, and 9. These results showed that ascorbic acid and rutin are complementary in their antioxidant actions, transport and signaling functions. Their combined antioxidant, antiinflammatory and antiapoptotic actions suggest rutin and ascorbic acid are a potentially cytoprotective team against UV-induced skin damage.

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The cross-talk between electrophiles, antioxidant defence and the endocannabinoid system in fibroblasts and keratinocytes after UVA and UVB irradiation

Cited by 64 publications

References 62 publications

Comparison of protective effect of ascorbic acid on redox and endocannabinoid systems interactions in in vitro cultured human skin fibroblasts exposed to UV radiation and hydrogen peroxide

Comparison of protective effect of ascorbic acid on redox and endocannabinoid systems interactions in in vitro cultured human skin fibroblasts exposed to UV radiation and hydrogen peroxide

Time-dependent effect of rutin on skin fibroblasts membrane disruption following UV radiation

Rutin and ascorbic acid cooperation in antioxidant and antiapoptotic effect on human skin keratinocytes and fibroblasts exposed to UVA and UVB radiation

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