A Powerful Mitochondria-Targeted Iron Chelator Affords High Photoprotection against Solar Ultraviolet A Radiation.
Ontology highlight
ABSTRACT:
SUBMITTER: Reelfs O
PROVIDER: S-EPMC4946793 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:UV radiation (UV) alters secondary metabolism in the skin of Vitis vinifera L. berries, which may affect on the final composition of both, grapes and wines. We compared berry skin transcriptome and phenolic composition between Tempranillo berries grown in the presence or absence of solar UV in a mid-altitude Tempranillo vineyard. By analysing two different ripening degrees, expression of 121 genes was significantly altered. Functional enrichment identified that, principally, secondary metabolism-related transcripts were induced by UV, including VvFLS1, VvGT5 and VvGT6 flavonol biosynthetic genes induction. Concurrently, flavonol accumulation was the most evident impact of UV on the berry skin phenolic composition. Monoterpenoid biosynthetic transcripts were also up-regulated by UV, whereas induction of stilbenoid biosynthetic transcripts and stilbenes accumulation was probably induced by the joint action of UV and other condition under the UV-blocking filter, likely higher temperature. Among regulatory genes, VvMYBF1, VvMYB24 and three bHLH transcription factors were up-regulated by UV. Homologs to Arabidopsis UVR8-dependent UV-B-induced genes were also induced, including VvHY5-1, VvHY5-2 and VvRUP UV-B signalling genes. This suggests that the UV-B-specific signalling pathway is activated in the skin of grapes grown at low-medium altitudes. The biosynthesis and accumulation of UV-absorbing compounds that are appreciated for winemaking were almost specifically triggered, which indicates that viticultural practices increasing solar UV incidence may improve grape features important to wine production.
2014-09-09 | GSE54636 | GEO
Project description:Eltrombopag (ELT) is a thrombopoietin receptor agonist reported to decrease labile iron in leukemia cells. Here we examine the previously undescribed iron(III)-coordinating and cellular iron-mobilizing properties of ELT. We find a high binding constant for iron(III) (log β2=35). Clinically achievable concentrations (1 µM) progressively mobilized cellular iron from hepatocyte, cardiomyocyte, and pancreatic cell lines, rapidly decreasing intracellular reactive oxygen species (ROS) and also restoring insulin secretion in pancreatic cells. Decrements in cellular ferritin paralleled total cellular iron removal, particularly in hepatocytes. Iron mobilization from cardiomyocytes exceeded that obtained with deferiprone, desferrioxamine, or deferasirox at similar iron-binding equivalents. When combined with these chelators, ELT enhanced cellular iron mobilization more than additive (synergistic) with deferasirox. Iron-binding speciation plots are consistent with ELT donating iron to deferasirox at clinically relevant concentrations. ELT scavenges iron citrate species faster than deferasirox, but rapidly donates the chelated iron to deferasirox, consistent with a shuttling mechanism. Shuttling is also suggested by enhanced cellular iron mobilization by ELT when combined with the otherwise ineffective extracellular hydroxypyridinone chelator, CP40. We conclude that ELT is a powerful iron chelator that decreases cellular iron and further enhances iron mobilization when combined with clinically available chelators.
| S-EPMC6558288 | biostudies-literature
Project description:UV radiation (UV) alters secondary metabolism in the skin of Vitis vinifera L. berries, which may affect on the final composition of both, grapes and wines. We compared berry skin transcriptome and phenolic composition between Tempranillo berries grown in the presence or absence of solar UV in a mid-altitude Tempranillo vineyard. By analysing two different ripening degrees, expression of 121 genes was significantly altered. Functional enrichment identified that, principally, secondary metabolism-related transcripts were induced by UV, including VvFLS1, VvGT5 and VvGT6 flavonol biosynthetic genes induction. Concurrently, flavonol accumulation was the most evident impact of UV on the berry skin phenolic composition. Monoterpenoid biosynthetic transcripts were also up-regulated by UV, whereas induction of stilbenoid biosynthetic transcripts and stilbenes accumulation was probably induced by the joint action of UV and other condition under the UV-blocking filter, likely higher temperature. Among regulatory genes, VvMYBF1, VvMYB24 and three bHLH transcription factors were up-regulated by UV. Homologs to Arabidopsis UVR8-dependent UV-B-induced genes were also induced, including VvHY5-1, VvHY5-2 and VvRUP UV-B signalling genes. This suggests that the UV-B-specific signalling pathway is activated in the skin of grapes grown at low-medium altitudes. The biosynthesis and accumulation of UV-absorbing compounds that are appreciated for winemaking were almost specifically triggered, which indicates that viticultural practices increasing solar UV incidence may improve grape features important to wine production. A total of 12 samples were hybridized. Grape skin RNA from berries ripening under a UV-transmitting filter (FUV+) and a UV-blocking filter (FUV-) was compared. Berry skin of two different ripening stages was analysed on each UV treatment. All samples were harvested simultaneously and a NaCl series was used to select the ripening degree in a non-invasive way. Three biological replicates were analyzed for each sample.
2014-09-09 | E-GEOD-54636 | biostudies-arrayexpress
Project description:BackgroundPathophysiology of rosacea is not completely understood and involves a complex interaction among genetics, ultraviolet (UV) light, microorganisms, impaired skin barrier, neuronal and vascular dysfunction, and immune system disruption.AimsTo describe the etiology of rosacea with an emphasis on the role of UV radiation and exposome, and to review the importance of non-pharmacologic strategies focusing on photoprotection.MethodsWe conducted a narrative review of the literature. We performed literature searches with PubMed from January 1990 to November 2020 using the keywords "rosacea", "pathogenesis", "ultraviolet radiation", "exposome", "photoprotection", "sunscreens" and "non-pharmacologic agents". The search was limited to English, Spanish, and French language articles.ResultsSeveral environmental factors such as UV light, diverse microorganisms, air pollution, tobacco smoking, nutrition, and psychological stress showed to trigger or worsen rosacea. UV radiation was reported to induce pro-inflammatory, pro-angiogenic, and pro-fibrotic responses. We found 6 original articles about the impact of sunscreens on rosacea. The use of sunscreens containing ingredients with emollient, anti-inflammatory, and/or vasoregulatory properties was shown to significantly improve symptomatology.ConclusionUV radiation and the exposome play a key role in the development of rosacea. UV light is implicated in all significant aspects of rosacea: skin inflammation, neoangiogenesis, telangiectasia, and fibrosis, and may even initiate rosacea. While the use of sunscreens is widely recommended, the literature on the impact of photoprotection in rosacea is scarce. Adequately formulated sunscreens could not only provide the required level of photoprotection, but may also help to mitigate the barrier dysfunction, neutralize facial redness (tinted sunscreens), and decrease inflammation and vascular dysfunction.
| S-EPMC8596706 | biostudies-literature
Project description:A current threat to the marine ecosystem is the high level of solar ultraviolet radiation (UV). Large whales have recently been shown to suffer sun-induced skin damage from continuous UV exposure. Genotoxic consequences of such exposure remain unknown for these long-lived marine species, as does their capacity to counteract UV-induced insults. We show that UV exposure induces mitochondrial DNA damage in the skin of seasonally sympatric fin, sperm, and blue whales and that this damage accumulates with age. However, counteractive molecular mechanisms are markedly different between species. For example, sperm whales, a species that remains for long periods at the sea surface, activate genotoxic stress pathways in response to UV exposure whereas the paler blue whale relies on increased pigmentation as the season progresses. Our study also shows that whales can modulate their responses to fluctuating levels of UV, and that different evolutionary constraints may have shaped their response strategies.
| S-EPMC3757271 | biostudies-other
Project description:The transcription factor Nrf2 determines the ability to adapt and survive under conditions of electrophilic, oxidative, and inflammatory stress by regulating the expression of elaborate networks comprising nearly 500 genes encoding proteins with versatile cytoprotective functions. In mice, disruption of Nrf2 increases susceptibility to carcinogens and accelerates disease pathogenesis. Paradoxically, Nrf2 is upregulated in established human tumors, but whether this upregulation drives carcinogenesis is not known. Here we show that the incidence, multiplicity, and burden of solar-simulated UV radiation-mediated cutaneous tumors that form in SKH-1 hairless mice in which Nrf2 is genetically constitutively activated are lower than those that arise in their wild-type counterparts. Pharmacologic Nrf2 activation by topical biweekly applications of small (40 nmol) quantities of the potent bis(cyano enone) inducer TBE-31 has a similar protective effect against solar-simulated UV radiation in animals receiving long-term treatment with the immunosuppressive agent azathioprine. Genetic or pharmacologic Nrf2 activation lowers the expression of the pro-inflammatory factors IL6 and IL1?, and COX2 after acute exposure of mice to UV radiation. In healthy human subjects, topical applications of extracts delivering the Nrf2 activator sulforaphane reduced the degree of solar-simulated UV radiation-induced skin erythema, a quantifiable surrogate endpoint for cutaneous damage and skin cancer risk. Collectively, these data show that Nrf2 is not a driver for tumorigenesis even upon exposure to a very potent and complete carcinogen and strongly suggest that the frequent activation of Nrf2 in established human tumors is a marker of metabolic adaptation.
| S-EPMC4454593 | biostudies-literature
Project description:This article describes data on the intensity of ultraviolet B (UVB) radiation collected during field questionnaire-based surveys in Athens, Greece. The surveys were conducted over 11 days of July and October 2010 at three different urban, outdoor sites. A total of 1104 interviews were conducted. The participants were asked to report whether they felt they got a sunburn at the moment of the interview. Questions related to personal characteristics including skin type and exposure time (visit duration at the interview site) were also included in the questionnaire.
| S-EPMC5358949 | biostudies-literature
Project description:BACKGROUND:A protective relationship has been hypothesized between exposure to solar ultraviolet radiation (UVR) and the development of breast cancer. OBJECTIVE:The objective of this study was to conduct a systematic literature review and meta-analysis of studies examining the association of exposure to solar UVR and breast cancer risk. METHODS:We searched Medline, EMBASE, and Web of Science for all studies investigating exposure to solar UVR and breast cancer risk. Separate analyses were performed using estimates of time spent in the sun, and ambient UVR. Associations were estimated using DerSimonian and Laird random-effect models. Heterogeneity was investigated through subgroup analyses and I2 statistics. RESULTS:Fourteen studies were included in the review and 13 in the meta-analysis, with the majority (n=8) conducted in North America. We observed a decreased risk of breast cancer for individuals spending ?1h/d in the sun during summer months over a lifetime or usual adulthood compared with <1h/d [pooled?relative?risk?(RR)=0.84; 95% CI: 0.77, 0.91]. Spending ?2h/d in the sun had a similar protective effect as 1 to <2h/d when compared with <1h/d (RR=0.83; 95% CI: 0.75, 0.93 vs. 0.83; 95% CI: 0.78, 0.89). Exposure during adolescence was suggestive of a lower risk of breast cancer than exposure later in life (?45?years of age) (RR=0.83; 95% CI: 0.71, 0.98 vs. 0.97; 95% CI: 0.85, 1.11). Ambient UVR was not associated with the risk of breast cancer (RR=1.00; 95% CI: 0.93, 1.09). DISCUSSION:To our knowledge, this was the first meta-analysis to estimate the risk of developing breast cancer associated with time spent in the sun. The results suggest that obtaining greater than an hour a day in the sun during the summer months could decrease the risk of developing breast cancer. https://doi.org/10.1289/EHP4861.
| S-EPMC7015554 | biostudies-literature
Project description:Ultraviolet (UV) irradiation is the leading factor in the development of skin cancer, prompting great interest in chemopreventive agents for this disease. In this study, we report the discovery of norathyriol, a plant-derived chemopreventive compound identified through an in silico virtual screening of the Chinese Medicine Library. Norathyriol is a metabolite of mangiferin found in mango, Hypericum elegans, and Tripterospermum lanceolatum and is known to have anticancer activity. Mechanistic investigations determined that norathyriol acted as an inhibitor of extracellular signal-regulated kinase (ERK)1/2 activity to attenuate UVB-induced phosphorylation in mitogen-activated protein kinases signaling cascades. We confirmed the direct and specific binding of norathyriol with ERK2 through a cocrystal structural analysis. The xanthone moiety in norathyriol acted as an adenine mimetic to anchor the compound by hydrogen bonds to the hinge region of the protein ATP-binding site on ERK2. Norathyriol inhibited in vitro cell growth in mouse skin epidermal JB6 P+ cells at the level of G(2)-M phase arrest. In mouse skin tumorigenesis assays, norathyriol significantly suppressed solar UV-induced skin carcinogenesis. Further analysis indicated that norathyriol mediates its chemopreventive activity by inhibiting the ERK-dependent activity of transcriptional factors AP-1 and NF-?B during UV-induced skin carcinogenesis. Taken together, our results identify norathyriol as a safe new chemopreventive agent that is highly effective against development of UV-induced skin cancer.
| S-EPMC3251698 | biostudies-literature
Project description:The relationship between solar ultraviolet radiation and the risk of breast cancer is conflicting. The purpose of our study was to quantitatively assess the relationship between solar ultraviolet radiation and breast cancer risk and to analyze related factors such as age and sunscreen use.Articles indexed in PubMed and Embase and published between January 2005 and March 2020 were searched for relevant keywords. The relative risk was calculated using random-effect or fixed-effect models in the meta-analysis and dose-response meta-analysis, which were conducted according to the Meta-Analyses of Observational Studies in Epidemiology reporting guidelines. Sensitivity analyses for heterogeneity and publication bias were evaluated.Six studies were eligible for inclusion in the meta-analysis, and three of these were included in the dose-response analysis. We found a correlation between exposure to solar ultraviolet radiation and breast cancer risk (relative risk: 0.70, 95% confidence interval: 0.65, 0.75). We also found a linear dose-response relationship between the exposure and breast cancer risk (relative risk: 0.86, 95% confidence interval: 0.81, 0.91) in women over 40. Not tanning and covering the limbs were associated with breast cancer risk, but sunscreen use was not.Exposure to solar ultraviolet radiation is negatively correlated with breast cancer risk, and the association is linear in women over 40. This is the first dose-response meta-analysis on the topic, and the influence of factors such as estrogen receptor status, occupational exposure, and ethnicity requires in-depth study.
| S-EPMC7647621 | biostudies-literature