scholarly journals Cytoprotective Effect of Ascorbic Acid and Rutin against Oxidative Changes in the Proteome of Skin Fibroblasts Cultured in a Three-Dimensional System

Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1074 ◽  
Author(s):  
Agnieszka Gęgotek ◽  
Iwona Jarocka-Karpowicz ◽  
Elżbieta Skrzydlewska

The combination of ascorbic acid and rutin, commonly used in oral preparations for their antioxidant and anti-inflammatory properties, can also be used to protect skin cells from the effects of UV radiation in sunlight. Here, we tested the potential protective effect of ascorbic acid and rutin used together in UVB-irradiated human skin fibroblasts, and assessed the proteomic profile of these cells, grown in a three-dimensional (3D) system. Proteomic findings revealed a combined effect of ascorbic acid and rutin in UV-irradiated fibroblasts against overexpression of pro-inflammatory signaling proteins and DNA reorganization/expression. These effects were not observed when cells were treated with either compounds alone. The antioxidant effects of ascorbic acid and rutin also prevented protein modifications by lipid peroxidation products. Further, ascorbic acid stimulated rutin-protein adduct formation, which supports intra/extracellular signaling and the Nrf2/ARE antioxidant pathway, contributing to the protective effects against UV-induced oxidative stress. The combined effect of ascorbic acid and rutin suggests that this combination of compounds is potentially effective against skin damage caused by UV radiation.

Antioxidants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 578
Author(s):  
Agnieszka Gęgotek ◽  
Wojciech Łuczaj ◽  
Elżbieta Skrzydlewska

Ultraviolet (UV) radiation is one of the primary factors responsible for disturbances in human skin cells phospholipid metabolism. Natural compounds that are commonly used to protect skin, due to their lipophilic or hydrophilic nature, show only a narrow range of cytoprotective activity, which prompts research on their combined application. Therefore, the aim of this study was to examine the effect of ascorbic acid and rutin on the phospholipid and ceramide profiles in UV-irradiated fibroblasts cultured in a three-dimensional system that approximates the culture conditions to the dermis. An ultra-high-performance liquid chromatograph coupled with a quadrupole time-of-flight mass spectrometer was used for phospholipid and ceramide profiling. As a result of UVA and UVB cells irradiation, upregulation of phosphatidylcholines, ceramides, and downregulation of sphingomyelins were observed, while treatment with ascorbic acid and rutin of UVA/UVB-irradiated fibroblast promoted these changes to provide cells a stronger response to stress. Moreover, an upregulation of phosphatidylserines in cells exposed to UVB and treated with both antioxidants suggests the stimulation of UV-damaged cells apoptosis. Our findings provide new insight into action of rutin and ascorbic acid on regulation of phospholipid metabolism, which improves dermis fibroblast membrane properties.


Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2672 ◽  
Author(s):  
Agnieszka Gęgotek ◽  
Iwona Jarocka-Karpowicz ◽  
Elżbieta Skrzydlewska

The combination of ascorbic acid and rutin, often used in oral preparations, due to antioxidant and anti-inflammatory properties, can be used to protect skin cells against the effects of UV radiation from sunlight. Therefore, the aim of this study was to investigate the synergistic effect of rutin and ascorbic acid on the proteomic profile of UVA and UVB irradiated keratinocytes cultured in a three-dimensional (3D) system. Results showed that the combination of rutin and ascorbic acid protects skin cells against UV-induced changes. In particular, alterations were observed in the expression of proteins involved in the antioxidant response, DNA repairing, inflammation, apoptosis, and protein biosynthesis. The combination of rutin and ascorbic acid also showed a stronger cytoprotective effect than when using either compound alone. Significant differences were visible between rutin and ascorbic acid single treatments in the case of protein carboxymethylation/carboxyethylation. Ascorbic acid prevented UV or rutin-induced protein modifications. Therefore, the synergistic effect of rutin and ascorbic acid creates a potentially effective protective system against skin damages caused by UVA and UVB radiation.


2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Agnieszka Gęgotek ◽  
Pedro Domingues ◽  
Elżbieta Skrzydlewska

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.


Author(s):  
Ok Kyung Kim ◽  
Da-Eun Nam ◽  
Min-Jae Lee ◽  
Namgil Kang ◽  
Jae-Youn Lim ◽  
...  

2020 ◽  
Vol 295 (8) ◽  
pp. 2483-2494
Author(s):  
Hiroyuki Yoshida ◽  
Mika Aoki ◽  
Aya Komiya ◽  
Yoko Endo ◽  
Keigo Kawabata ◽  
...  

The immune-regulatory compound histamine is involved in the metabolism of the essential skin component hyaluronan (HA). We previously reported that histamine up-regulates the expression of HYBID (hyaluronan-binding protein involved in hyaluronan depolymerization, also called CEMIP or KIAA1199), which plays a key role in HA degradation. However, no information is available about histamine's effects on HA synthase (HAS) expression, the molecular sizes of HA species produced, and histamine receptors and their signaling pathways in skin fibroblasts. Moreover, histamine's effects on photoaged skin remain elusive. Here, we show that histamine increases HA degradation by up-regulating HYBID and down-regulating HAS2 in human skin fibroblasts in a dose- and time-dependent manner and thereby decreases the total amounts and sizes of newly produced HA. Histamine H1 blocker abrogated the histamine effects on HYBID up-regulation, HAS2 suppression, and HA degradation. Histamine H1 agonist exhibited effects on HA levels, composition, and breakdown similar to those of histamine. Of note, blockade of protein kinase Cδ or PI3K–Akt signaling abolished histamine-mediated HYBID stimulation and HAS2 suppression, respectively. Immunohistochemical experiments revealed a significant ∼2-fold increase in tryptase-positive mast cells in photoaged skin, where HYBID and HAS2 expression levels were increased and decreased, respectively, compared with photoprotected skin. These results indicate that histamine controls HA metabolism by up-regulating HYBID and down-regulating HAS2 via distinct signaling pathways downstream of histamine receptor H1. They further suggest that histamine may contribute to photoaged skin damage by skewing HA metabolism toward degradation.


2020 ◽  
Vol 2020 (9) ◽  
Author(s):  
Rodolfo Panerai ◽  
Antonio Pittelli ◽  
Konstantina Polydorou

Abstract We find a one-dimensional protected subsector of $$ \mathcal{N} $$ N = 4 matter theories on a general class of three-dimensional manifolds. By means of equivariant localization we identify a dual quantum mechanics computing BPS correlators of the original model in three dimensions. Specifically, applying the Atiyah-Bott-Berline-Vergne formula to the original action demonstrates that this localizes on a one-dimensional action with support on the fixed-point submanifold of suitable isometries. We first show that our approach reproduces previous results obtained on S3. Then, we apply it to the novel case of S2× S1 and show that the theory localizes on two noninteracting quantum mechanics with disjoint support. We prove that the BPS operators of such models are naturally associated with a noncom- mutative star product, while their correlation functions are essentially topological. Finally, we couple the three-dimensional theory to general $$ \mathcal{N} $$ N = (2, 2) surface defects and extend the localization computation to capture the full partition function and BPS correlators of the mixed-dimensional system.


Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 1931
Author(s):  
Glenda Calniquer ◽  
Marina Khanin ◽  
Hilla Ovadia ◽  
Karin Linnewiel-Hermoni ◽  
David Stepensky ◽  
...  

Oral carotenoids and polyphenols have been suggested to induce photo-protective effects. The aim of the study was to test whether the combination of carotenoids and polyphenols produce greater protective effects from UV-induced damage to skin cells. Such damage is characterized by inflammation and oxidative stress; thus, the photo-protective effect can be partially explained by modulating the nuclear factor kappa B (NFκB) and antioxidant response element/Nrf2 (ARE/Nrf2) transcription systems, known as important regulators of these two processes. Indeed, it was found in keratinocytes that carotenoids and polyphenols inhibit UVB-induced NFκB activity and release of cytokine IL-6. A combination of tomato extract with rosemary extract inhibited UVB-induced release of IL-6 more than each of the compounds alone. Moreover, this combination synergistically activated ARE/Nrf2 transcription systems. Inflammatory cytokines such as IL-6 and TNFα induce the expression of matrix metalloproteinases (MMPs), which leads to collagen breakdown; thus, it is important to note that carnosic acid reduced TNFα-induced MMP-1 secretion from human dermal fibroblasts. The in vitro results suggest beneficial effects of phytonutrient combinations on skin health. To assure that clinical experiments to prove such effects in humans are feasible, the human bioavailability of carotenoids from tomato extract was tested, and nearly a twofold increase in their plasma concentrations was detected. This study demonstrates that carotenoids and polyphenols cooperate in balancing UV-induced skin cell damage, and suggests that NFκB and ARE/Nrf2 are involved in these effects.


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