FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2783010290> ?p ?o ?g. }

• W2783010290 endingPage "251" @default.
• W2783010290 startingPage "248" @default.
• W2783010290 abstract "Acute exposure of skin to UV-B causes DNA damage and sunburn erythema in both mice and humans. Previous studies documented time-of-day-related differences in sunburn responses after UV-B exposure in mice. Because humans are diurnal and mice are nocturnal, the circadian rhythm in human skin was hypothesized to be in opposite phase to the rhythm in mice. A study by Nikkola et al. demonstrates that humans are more prone to sunburn erythema after evening exposure to solar UV-B radiation as compared with morning exposure. Acute exposure of skin to UV-B causes DNA damage and sunburn erythema in both mice and humans. Previous studies documented time-of-day-related differences in sunburn responses after UV-B exposure in mice. Because humans are diurnal and mice are nocturnal, the circadian rhythm in human skin was hypothesized to be in opposite phase to the rhythm in mice. A study by Nikkola et al. demonstrates that humans are more prone to sunburn erythema after evening exposure to solar UV-B radiation as compared with morning exposure. Because mice are nocturnal and humans are diurnal, their circadian clock outputs are out of phase. Based on this argument, and previous data relating time-of-day UV exposure to severity of UV effects in mouse skin, it was proposed that humans would be more prone to sunburn after late afternoon UV exposure rather than morning exposure.The majority of living organisms on the Earth are photosensitive and are influenced by the solar day and night cycle created by the axial rotation of the Earth. Consequently, cells have developed an amazing time-keeping mechanism known as the circadian clock that is self-sustained and oscillates with a periodic cycle of approximately 24 hours. In mammals, the molecular clock is entrained daily by the morning sunlight entering the eyes to reset the master clock located in the suprachiasmatic nucleus of the brain. The suprachiasmatic nucleus, via various hormonal and neuronal signals, synchronizes peripheral tissues including the heart, lung, liver, and skin. At the molecular level, the circadian clock is made up of primary as well as secondary feedback loops that are primarily responsible for approximately 24-hour rhythmicity of clock-controlled genes. Proteins including brain and muscle ARNT-like protein 1 (BMAL1), circadian locomotor output kaput (CLOCK), cryptochromes (CRY 1, 2), and periods (PER 1, 2, 3) make up a transcriptional-translational feedback loop that is initiated by dimerization of BMAL1 and CLOCK and the subsequent binding of this complex to the E-Box sequence (CACGTG or CACGTT) found in the promoter region of target clock-controlled genes (Lowrey and Takahashi, 2011Lowrey P.L. Takahashi J.S. Genetics of circadian rhythms in Mammalian model organisms.Adv Genet. 2011; 74: 175-230Crossref PubMed Scopus (409) Google Scholar). Tissue-specific circadian expression patterns have been observed in as many as 10% of mammalian genes, and many of these genes regulate cell cycle, metabolism, cell death, and DNA repair processes (Sancar et al., 2015Sancar A. Lindsey-Boltz L.A. Gaddameedhi S. Selby C.P. Ye R. Chiou Y.Y. et al.Circadian clock, cancer, and chemotherapy.Biochemistry. 2015; 54: 110-123Crossref PubMed Scopus (109) Google Scholar). Because mice are nocturnal and humans are diurnal, their circadian clock outputs are out of phase. Based on this argument, and previous data relating time-of-day UV exposure to severity of UV effects in mouse skin, it was proposed that humans would be more prone to sunburn after late afternoon UV exposure rather than morning exposure. Apart from its life-giving quality, the Sun emits harmful UVR that induces DNA damage in skin. Exposure to UVR causes a plethora of skin-related issues including photoaging, sunburn erythema, and skin cancers including melanomas, the deadliest skin cancers. In recent years, the skin’s circadian clock has been shown to regulate various cellular responses after UVR exposure, including nucleotide excision repair, cell cycle checkpoints, oxidative stress, and apoptosis (Dakup and Gaddameedhi, 2017Dakup P. Gaddameedhi S. Impact of the circadian clock on UV-induced DNA damage response and photocarcinogenesis.Photochem Photobiol. 2017; 93: 296-303Crossref PubMed Scopus (37) Google Scholar, Gaddameedhi et al., 2011Gaddameedhi S. Selby C.P. Kaufmann W.K. Smart R.C. Sancar A. Control of skin cancer by the circadian rhythm.Proc Natl Acad Sci USA. 2011; 108: 18790-18795Crossref PubMed Scopus (163) Google Scholar, Geyfman et al., 2012Geyfman M. Kumar V. Liu Q. Ruiz R. Gordon W. Espitia F. et al.Brain and muscle Arnt-like protein-1 (BMAL1) controls circadian cell proliferation and susceptibility to UVB-induced DNA damage in the epidermis.Proc Natl Acad Sci USA. 2012; 109: 11758-11763Crossref PubMed Scopus (162) Google Scholar, Plikus et al., 2015Plikus M.V. Van Spyk E.N. Pham K. Geyfman M. Kumar V. Takahashi J.S. et al.The circadian clock in skin: implications for adult stem cells, tissue regeneration, cancer, aging, and immunity.J Biol Rhythms. 2015; 30: 163-182Crossref PubMed Scopus (103) Google Scholar, Sancar et al., 2015Sancar A. Lindsey-Boltz L.A. Gaddameedhi S. Selby C.P. Ye R. Chiou Y.Y. et al.Circadian clock, cancer, and chemotherapy.Biochemistry. 2015; 54: 110-123Crossref PubMed Scopus (109) Google Scholar, Wang et al., 2017Wang H. van Spyk E. Liu Q. Geyfman M. Salmans M.L. Kumar V. et al.Time-restricted feeding shifts the skin circadian clock and alters UVB-induced DNA damage.Cell Rep. 2017; 20: 1061-1072Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar). These robust protective mechanisms attenuate unwanted consequences of UVR-mediated DNA damage. Skin clock regulation of nucleotide excision repair has been well characterized using the SKH-1 hairless mouse model, where it was observed that an elevated rate of UV photoproduct removal correlated with higher expression of the core nucleotide excision repair factor Xpa in the evening as compared with the morning (Gaddameedhi et al., 2011Gaddameedhi S. Selby C.P. Kaufmann W.K. Smart R.C. Sancar A. Control of skin cancer by the circadian rhythm.Proc Natl Acad Sci USA. 2011; 108: 18790-18795Crossref PubMed Scopus (163) Google Scholar). However, acute exposure to UVR also causes a UV-induced inflammatory reaction that is characterized by vasodilation and increased blood flow to the dermis, resulting in sunburn erythema in the affected skin. Using SKH-1 hairless mice, we have shown that more sunburn erythema occurs in morning solar UV-B-treated mice than in evening-treated animals (Gaddameedhi et al., 2015Gaddameedhi S. Selby C.P. Kemp M.G. Ye R. Sancar A. The circadian clock controls sunburn apoptosis and erythema in mouse skin.J Invest Dermatol. 2015; 135: 1119-1127Abstract Full Text Full Text PDF PubMed Scopus (45) Google Scholar). We determined that during morning time, when DNA repair is lowest and DNA synthesis is highest, the DNA damage caused by UVR leads to stronger activation of the Atr protein kinase, which is known to be activated in response to replication stress and to regulate the stability of the tumor suppressor p53. This results in increased numbers of sunburn apoptotic cells and enhanced inflammation in mouse skin. Because mice are nocturnal and humans are diurnal, their circadian clock outputs are out of phase. Based on this argument, and previous data relating time-of-day UV exposure to severity of UV effects in mouse skin, it was proposed that humans would be more prone to sunburn after late afternoon UV exposure rather than morning exposure. Nikkola et al. evaluated the circadian time effect of narrow band-UV-B exposure on sunburn erythema in human skin. They selected 19 subjects (16 females and 3 males) having skin types II and III as defined by Fitzpatrick sun-reactive skin type scale (Fitzpatrick, 1988Fitzpatrick T.B. The validity and practicality of sun-reactive skin types I through VI.Arch Dermatol. 1988; 124: 869-871Crossref PubMed Scopus (3021) Google Scholar). Subjects were exposed to increasing doses of narrow band-UV-B up to 4 suberythemal dose, once in the morning between 7 am and 9 am on one buttock and once in the evening between 7 pm and 9 pm on the other buttock of the same subject. Twenty-four hours after UV-B treatment, the erythema of the skin patches was quantified and skin biopsies were irradiated with the highest dose of UV-B (i.e., 4 suberythemal dose = 40 mJ/cm2 CIE (Commission Internationale de l'Eclairage, Vienna, Austria)) were collected. Protein levels of the tumor suppressor proteins p53 and the clock proteins CRY1 and CRY2 were measured in biopsies. Interestingly, the authors found that human subjects treated with UV-B in the evening had a significantly higher erythema index scores in comparison with the subjects exposed in the morning. In addition, different levels of CRY1 and CRY2 were detected in irradiated skin using immunohistochemistry, and human subjects with a negligible amount of CRY2 showed more erythema relative to individuals with high levels of CRY2. This is a novel observation. The authors speculated that CRY2 protects against UV-B-mediated skin damage. In a different study, the Lamia group reported that CRY2 regulated c-MYC proteasomal degradation by acting as a cofactor for the SCF substrate adaptor FBXL3 (an E3 ligase protein) (Huber et al., 2016Huber A.L. Papp S.J. Chan A.B. Henriksson E. Jordan S.D. Kriebs A. et al.CRY2 and FBXL3 cooperatively degrade c-MYC.Mol Cell. 2016; 64: 774-789Abstract Full Text Full Text PDF PubMed Scopus (112) Google Scholar). Because c-MYC plays important roles in cell proliferation, cell growth, and apoptosis, high levels of CRY2 could enhance c-MYC degradation, which in turn might reduce sunburn-induced apoptosis and other characteristic features of sunburn erythema. It would be interesting to evaluate levels of core clock proteins including CRY1, 2, PER1, 2, 3, BMAL1, and CLOCK in a larger sample set. Also, knowing the chronotype (behavioral manifestation of the underlying biological clock) of the patients with negligible amount of CRY2 levels would facilitate understanding the effects of circadian clock disruption on sunburn erythema. Collectively, the above additional information would define mechanistic similarities and circadian phase output differences between human and mouse models as shown in Figure 1. In addition to CRY protein levels, Nikkola et al. also measured p53 concentrations in skin biopsies and observed increased p53 levels in the morning samples compared with the evening group. This observation appears to contradict the predicted human skin sunburn model, but the authors suggested that the possible reasons for this observation were either delayed (24 hours after UV-B irradiation) biopsy collection in comparison with the mouse study previously conducted by us or a dissociation of human p53 elevation and erythema as previously suggested (Healy et al., 1994Healy E. Reynolds N.J. Smith M.D. Campbell C. Farr P.M. Rees J.L. Dissociation of erythema and p53 protein expression in human skin following UVB irradiation, and induction of p53 protein and mRNA following application of skin irritants.J Invest Dermatol. 1994; 103: 493-499Abstract Full Text PDF PubMed Google Scholar). However, the paper by Healy et al. did not consider the circadian aspect of p53 and erythema, nor were subjects selected according to chronotype. Thus, the observations by Healy et al. may not be directly relatable to the current study. In contrast, strong evidence of p53 involvement in sunburn erythema was shown by Brash’s group using p53 knockout mouse models, where they demonstrated that deleting p53 gene in mouse skin decreased the number of sunburn-mediated apoptotic cells after exposure to UV-B (Ziegler et al., 1994Ziegler A. Jonason A.S. Leffell D.J. Simon J.A. Sharma H.W. Kimmelman J. et al.Sunburn and p53 in the onset of skin cancer.Nature. 1994; 372: 773-776Crossref PubMed Scopus (1348) Google Scholar). In another recent paper (Guan et al., 2016Guan L. Suggs A. Ahsanuddin S. Tarrillion M. Selph J. Lam M. et al.2016 Arte poster competition first place winner: circadian rhythm and UV-induced skin damage: an in vivo study.J Drugs Dermatol. 2016; 15: 1124-1130PubMed Google Scholar) in which erythema induction was examined as a function of time-of-day of UV exposure, the authors reported enhanced erythema in human subjects after morning treatment in comparison with evening exposure. However, this study used solar simulated radiation, which is primarily composed of UV-A radiation that is much less efficient at inducing canonical UV bipyrimidine dimers in DNA, rather than narrow band-UV-B as in the Nikkola et al. study. Guan et al. also did not evaluate core clock gene expression levels in skin biopsies of the subjects, which is important to understand the circadian phase of the observations. In future studies, it will be interesting to determine how different experimental parameters and variables in the Guan et al. and Nikkola et al. studies contribute to the unique time-of-day erythemal responses in humans. It should be noted that there are additional factors that may contribute to circadian effects on UV responses in human skin, such as skin type, sleep cycles, and feeding behaviors of the participating human volunteers. These issues are more difficult to control for in human studies than in mice. In a recent elegant study, the Andersen group showed that restricting feeding to the inactive phase (during day time) in mice shifts the skin’s circadian clock and its response to solar UV-B irradiation (Wang et al., 2017Wang H. van Spyk E. Liu Q. Geyfman M. Salmans M.L. Kumar V. et al.Time-restricted feeding shifts the skin circadian clock and alters UVB-induced DNA damage.Cell Rep. 2017; 20: 1061-1072Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar). The group concluded that daytime feeding reverses diurnal sensitivity to UVB-induced DNA damage specifically by influencing the oscillatory expression pattern of the Xpa gene. Feeding and social behaviors of human subjects may also affect UV responses and should therefore be considered when designing future studies involving humans. A few possible solutions to this problem include evaluating participating human subjects in sleep research labs, where their sleep cycles, physical activity, and feeding patterns can be closely monitored, or formulating detailed questionnaires for the volunteers at the time of enrollment. Collectively, the Nikkola et al. and Guan et al. papers show involvement of circadian timing in UVR-induced sunburn erythema in humans, but report different observations relating the intensity of sunburn erythema to time-of-day UVR exposure. Observations of core clock gene expression pattern in the −/+UV-B-treated skin samples bolster the involvement of circadian clock regulation in UV-B-induced sunburn erythema in humans. However, it would have been fascinating to perform additional mechanistic studies to understand the signaling events occurring through the skin’s circadian clock on UVR exposure and correlate the results with the observed phenotype in humans. Our environment is constantly changing, challenging us both socially and biologically, and pushing us to adopt erratic time schedules. Irregular and unhealthy sleep cycles and feeding patterns are disrupting our natural circadian rhythm and making us vulnerable to environmental stresses that vary depending on the time-of-day. Despite the strong evidence that the circadian clock impacts on sunburn erythema in mice, there are still active debate about the vulnerability of human skin to UVR-induced erythema as a function of the time-of-day of exposure. One reason for continued controversy could be huge variations in the natural rhythm among humans, which make such studies much more difficult and time consuming. Hence, special efforts should be made to select appropriate human volunteers. Identification of the optimal time-of-day to minimize sunburn erythema in humans may soon be possible, and may be consistent with the model proposed by Gaddameedhi et al., 2015Gaddameedhi S. Selby C.P. Kemp M.G. Ye R. Sancar A. The circadian clock controls sunburn apoptosis and erythema in mouse skin.J Invest Dermatol. 2015; 135: 1119-1127Abstract Full Text Full Text PDF PubMed Scopus (45) Google Scholar. Until then, minimization of sun exposure and photoprotection should continue to be recommended. The authors state no conflict of interest. The authors thank Dr Michael G. Kemp at Wright State University and Panshak Dakup at WSU for critical reading of this commentary. SG was supported by National Institutes of Health grant 4R00ES022640 and WSU College of Pharmacy. Circadian Time Effects on NB-UVB–Induced Erythema in Human Skin In VivoJournal of Investigative DermatologyVol. 138Issue 2PreviewUVR-induced skin erythema occurs after DNA damage, a consequence of the cell signaling cascades and synthesis of various cytokines and inflammatory mediators detected as vasodilation, inflammation, and apoptosis (Sklar et al., 2013). UVB-induced carcinogenesis has been linked to circadian time in mice, because those subjected to chronic UVB radiation in the morning had a 5-fold higher number of invasive squamous cell carcinomas compared with the evening-treated group (Gaddameedhi et al., 2011). Full-Text PDF Open Archive" @default.
• W2783010290 created "2018-01-26" @default.
• W2783010290 creator A5029196238 @default.
• W2783010290 creator A5050158902 @default.
• W2783010290 date "2018-02-01" @default.
• W2783010290 modified "2023-10-15" @default.
• W2783010290 title "UV-B-Induced Erythema in Human Skin: The Circadian Clock Is Ticking" @default.
• W2783010290 cites W1569437915 @default.
• W2783010290 cites W1976796682 @default.
• W2783010290 cites W1993358791 @default.
• W2783010290 cites W2004063201 @default.
• W2783010290 cites W2139560874 @default.
• W2783010290 cites W2139669192 @default.
• W2783010290 cites W2147704658 @default.
• W2783010290 cites W2155667080 @default.
• W2783010290 cites W2551168273 @default.
• W2783010290 cites W2554328824 @default.
• W2783010290 cites W2739538381 @default.
• W2783010290 cites W2746590583 @default.
• W2783010290 cites W4250928742 @default.
• W2783010290 doi "https://doi.org/10.1016/j.jid.2017.09.002" @default.
• W2783010290 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29389325" @default.
• W2783010290 hasPublicationYear "2018" @default.
• W2783010290 type Work @default.
• W2783010290 sameAs 2783010290 @default.
• W2783010290 citedByCount "13" @default.
• W2783010290 countsByYear W27830102902018 @default.
• W2783010290 countsByYear W27830102902019 @default.
• W2783010290 countsByYear W27830102902020 @default.
• W2783010290 countsByYear W27830102902021 @default.
• W2783010290 countsByYear W27830102902022 @default.
• W2783010290 countsByYear W27830102902023 @default.
• W2783010290 crossrefType "journal-article" @default.
• W2783010290 hasAuthorship W2783010290A5029196238 @default.
• W2783010290 hasAuthorship W2783010290A5050158902 @default.
• W2783010290 hasBestOaLocation W27830102901 @default.
• W2783010290 hasConcept C121446783 @default.
• W2783010290 hasConcept C126322002 @default.
• W2783010290 hasConcept C16005928 @default.
• W2783010290 hasConcept C2777459323 @default.
• W2783010290 hasConcept C2779121184 @default.
• W2783010290 hasConcept C38606739 @default.
• W2783010290 hasConcept C54355233 @default.
• W2783010290 hasConcept C71924100 @default.
• W2783010290 hasConcept C86803240 @default.
• W2783010290 hasConceptScore W2783010290C121446783 @default.
• W2783010290 hasConceptScore W2783010290C126322002 @default.
• W2783010290 hasConceptScore W2783010290C16005928 @default.
• W2783010290 hasConceptScore W2783010290C2777459323 @default.
• W2783010290 hasConceptScore W2783010290C2779121184 @default.
• W2783010290 hasConceptScore W2783010290C38606739 @default.
• W2783010290 hasConceptScore W2783010290C54355233 @default.
• W2783010290 hasConceptScore W2783010290C71924100 @default.
• W2783010290 hasConceptScore W2783010290C86803240 @default.
• W2783010290 hasIssue "2" @default.
• W2783010290 hasLocation W27830102901 @default.
• W2783010290 hasOpenAccess W2783010290 @default.
• W2783010290 hasPrimaryLocation W27830102901 @default.
• W2783010290 hasRelatedWork W2041844070 @default.
• W2783010290 hasRelatedWork W2049390878 @default.
• W2783010290 hasRelatedWork W2090209293 @default.
• W2783010290 hasRelatedWork W2109327145 @default.
• W2783010290 hasRelatedWork W2140682486 @default.
• W2783010290 hasRelatedWork W2153916146 @default.
• W2783010290 hasRelatedWork W2395497249 @default.
• W2783010290 hasRelatedWork W3136837454 @default.
• W2783010290 hasRelatedWork W3195765690 @default.
• W2783010290 hasRelatedWork W4285097245 @default.
• W2783010290 hasVolume "138" @default.
• W2783010290 isParatext "false" @default.
• W2783010290 isRetracted "false" @default.
• W2783010290 magId "2783010290" @default.
• W2783010290 workType "article" @default.