The Differences in the Proteome Profile of Cannabidiol-Treated Skin Fibroblasts following UVA or UVB Irradiation in 2D and 3D Cell Cultures

Gęgotek, Agnieszka; Atalay, Sinemyiz; Domingues, Pedro; Skrzydlewska, Elżbieta

doi:10.3390/cells8090995

Cited by 52 publications

(67 citation statements)

References 50 publications

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“…Additionally, the level of 4-HNE-protein adducts is increased in the keratinocytes of psoriatic patients. The formation of 4-HNE-protein adducts in psoriatic keratinocytes has already been demonstrated in proteomics studies, especially in the context of proteins involved in the antioxidant response [78]. The intensification of the lipid peroxidation process was also observed in the blood cells and plasma of patients with psoriasis vulgaris [49,50], which confirms that this disease, regardless of local metabolic modifications in skin cells, is also characterized by changes in systemic metabolism.…”

Section: Phospholipid Metabolism In Keratinocytes Treated With Cbdsupporting

confidence: 57%

Cannabidiol Effects on Phospholipid Metabolism in Keratinocytes from Patients with Psoriasis Vulgaris

Jarocka-Karpowicz

Biernacki

Wroński³

et al. 2020

Biomolecules

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101

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Psoriasis is a chronic inflammatory skin disease characterized by dysregulated keratinocyte differentiation, but oxidative stress also plays an important role in the pathogenesis of this disease. Here, we examined the effect of cannabidiol (CBD), a phytocannabinoid with antioxidant and anti-inflammatory properties, on the redox balance and phospholipid metabolism in UVA/UVB-irradiated keratinocytes isolated from the skin of psoriatic patients or healthy volunteers. CBD accumulates mainly in membrane keratinocytes, especially from patients with psoriasis. This phytocannabinoid reduces the redox imbalance observed in the UV-irradiated keratinocytes of healthy subjects. It does so by decreasing reactive oxygen species (ROS) generation, increasing the Trx-dependent system efficiency, and increasing vitamin A and E levels. Consequently, a reduction in lipid peroxidation products, such as 8-isoprostanes and 4-hydroxynonenal, was also observed. Moreover, CBD modifies redox balance and lipid peroxidation in psoriatic patient keratinocytes following UV-irradiation. Interestingly, these changes are largely in the opposite direction to the case of keratinocytes from healthy subjects. CBD also regulates metabolic changes by modulating the endocannabinoid system that is disturbed by psoriasis development and UV irradiation. We observed a decrease in anandamide level in the UV-irradiated keratinocytes of healthy controls following CBD treatment, while in keratinocytes from patients treated with CBD, anandamide level was increased. However, the level of palmitoylethanolamide (PEA) was decreased in both groups treated with CBD. We further demonstrate that CBD increases CB1 receptor expression, primarily in the keratinocytes of patients, and increases CB2 receptor expression in both the psoriatic and control groups. However, CBD decreases CB2 receptor expression in UV-irradiated keratinocytes taken from patients. The UV- and psoriasis-induced activity of transmembrane transporters (Multidrug-Resistance (MDR) and breast cancer resistance protein (BCRP)) is normalized after CBD treatment. We conclude that CBD partially reduces oxidative stress in the keratinocytes of healthy individuals, while showing a tendency to increase the oxidative and inflammatory state in the keratinocytes of patients with psoriasis, especially following UV-irradiation.

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Section: Phospholipid Metabolism In Keratinocytes Treated With Cbdsupporting

confidence: 57%

Cannabidiol Effects on Phospholipid Metabolism in Keratinocytes from Patients with Psoriasis Vulgaris

Jarocka-Karpowicz

Biernacki

Wroński³

et al. 2020

Biomolecules

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101

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“…Although no effects of cannabidiolic acid were already reported in skin and skin cells, cannabidiol protective effects in dermatology are already investigated [ 34 ]. In particular cannabidiol was found to be able to activate antioxidant pathways both in fibroblasts and keratinocytes exposed to UV radiation and hydrogen peroxide [ 35 , 36 ] in accordance with the results from the MTT assay.…”

Section: Resultsmentioning

confidence: 53%

Metabolomic Profile and Antioxidant/Anti-Inflammatory Effects of Industrial Hemp Water Extract in Fibroblasts, Keratinocytes and Isolated Mouse Skin Specimens

et al. 2021

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Industrial hemp is a multiuse crop whose phytocomplex includes terpenophenolics and flavonoids. In the present study, the phenolic and terpenophenolic compounds were assayed in the water extract of the hemp variety Futura 75. Protective effects were also investigated in human fibroblast and keratinocytes and isolate mouse skin specimens, which were exposed to hydrogen peroxide and/or to the extract (1–500 µg/mL). The results of phytochemical analysis suggested the cannabidiol, cannabidiolic acid and rutin as the prominent phytocompounds. In the in vitro system represented by human keratinocytes and fibroblasts, the hemp extract was found to be able to protect cells from cytotoxicity and apoptosis induced by oxidative stress. Moreover, modulatory effects on IL-6, a key mediator in skin proliferation, were found. In isolated rat skin, the extract reduced hydrogen peroxide-induced l-dopa turnover, prostaglandin-E2 production and the ratio kynurenine/tryptpophan, thus corroborating anti-inflammatory/antioxidant effects. The in silico docking studies also highlighted the putative interactions between cannabidiol, cannabidiolic acid and rutin with tyrosinase and indoleamine-2,3-dioxygenase, involved in l-dopa turnover and tryptophan conversion in kynurenine, respectively. In conclusion, the present findings showed the efficacy of hemp water extract as a skin protective agent. This could be partly related to the extract content in cannabidiol, cannabidiolic acid and rutin.

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“…Moreover, to describe the changes that occur in UVA-irradiated skin cells, it is necessary to understand homeostasis not only at the cell level but also at the tissue level. The use of a three-dimensional cell culture model facilitates the observation of different layers of processes in the skin tissue, including changes in intracellular metabolism and intercellular signalling [ 34 – 36 ].…”

Section: Discussionmentioning

confidence: 99%

Natural Exogenous Antioxidant Defense against Changes in Human Skin Fibroblast Proteome Disturbed by UVA Radiation

Gęgotek

Domingues

2020

Oxidative Medicine and Cellular Longevity

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Daily exposure of the skin to UVA radiation causes oxidative modifications to cellular components and biomolecules. These include proteins involved in the metabolism and cytoprotection of fibroblasts, and their modification can contribute to the disruption of cell function and the development of skin disorders. Therefore, there remains a need for highly active cytoprotective compounds with antioxidant properties. The purpose of this study was to investigate the effect of ascorbic acid on the activity of rutin against UVA-induced changes in the proteome of human fibroblasts. All analyses were carried out on fibroblasts cultured in a three-dimensional system exposed to UVA radiation and incubated with rutin and ascorbic acid. Their proteomic profile was analyzed using nano-HPLC, which revealed 150 proteins whose expression was significantly altered between treatment conditions. UVA radiation led to changes in the expression of 82 proteins. However, some of these changes were mitigated by rutin and ascorbic acid separately (23 and 25 proteins, respectively) and rutin and ascorbic acid together (23 proteins). UVA radiation has led to the upregulation of proteins involved in gene expression, catalytic processes and antioxidant pathways, and downregulation of proteins with binding activity. Nevertheless, rutin and ascorbic acid used separately or together have countered these changes to varying degrees. Moreover, rutin and ascorbic acid stimulated fibroblasts irradiated by UVA to increase the expression of the signalling molecules responsible for the opening of the transmembrane channels. In the context of the results obtained, the observed cytoprotective effect of the cooperation of rutin and ascorbic acid results not only from the overlapping properties of the compounds. The effect of rutin alone is probably inhibited by its limited bioavailability. Therefore, its interaction with ascorbic acid increases membrane penetration and improves the cytoprotective effect on skin fibroblasts.

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The Differences in the Proteome Profile of Cannabidiol-Treated Skin Fibroblasts following UVA or UVB Irradiation in 2D and 3D Cell Cultures

Cited by 52 publications

References 50 publications

Cannabidiol Effects on Phospholipid Metabolism in Keratinocytes from Patients with Psoriasis Vulgaris

Cannabidiol Effects on Phospholipid Metabolism in Keratinocytes from Patients with Psoriasis Vulgaris

Metabolomic Profile and Antioxidant/Anti-Inflammatory Effects of Industrial Hemp Water Extract in Fibroblasts, Keratinocytes and Isolated Mouse Skin Specimens

Natural Exogenous Antioxidant Defense against Changes in Human Skin Fibroblast Proteome Disturbed by UVA Radiation

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