Background: Extrinsic aging results from environmental stressors such as UVR or pollutants. While the effects of single pollutants are better understood, those of their combination remain poorly scrutinized. Objective: Building on a study showing downregulation of several processes upon co-exposure to B[a]P and UVA, we investigated changes induced by epigenetic marks. MaterialsandMethods: Human primary fibroblasts and HaCaT cells were exposed to B[a]P and UVA. After 24 hours, exposed and unexposed cells were compared to assess DNA methylation. Focusing on HaCaT, multiplex assays enabled quantifying histone H3 modifications and evaluating four splicing factors (SRSF1, SRSF3, SFPQ, and SF3B1) by immunohistochemical labeling. The expression of keratinocyte-/fibroblast-relevant genes was assessed by RT-qPCR. Finally, the impact of an Arundodonax L. extract added 24 hours before B[a]P-UVA co-exposure was analyzed. Results: Exposure to B[a]P-UVA raised DNA methylation (HaCaT: ×3.6, fibroblasts: ×1.9), an increase prevented by the extract. In HaCaT cells, B[a]P-UVA increases the frequency of S10P (+38%). When exposure was preceded by extract treatment, the frequency of several methylations was impacted. B[a]P-UVA only induced the expression of SRSF1 and SFPQ in HaCaT (+46% and +34%). Treatment with the extract abolished this effect. Co-exposure increases the expression of inflammation-related genes (IL-1α, IL-1β) in HaCaT cells and decreases those of AQP3, KRT15, and SOD2. The extract has little effect on these changes. In primary fibroblasts, exposure to B[a]P-UVA lowered the expression of LOXL2, LUM, and TGFBR2 (？38%, ？59%, and ？51%, respectively), and the extract did not affect these modifications. Conclusion: Within 24 hours, a single B[a]P-UVA co-exposure changes epigenetic marks of skin cells but has only mild effects on gene expression. An Arundodonax L. extract can prevent part of the epigenetic marks’ changes and could stimulate the expression of some genes in primary fibroblasts.
References
[1]
Farage, M.A., Miller, K.W., Elsner, P. and Maibach, H.I. (2008) Intrinsic and Extrinsic Factors in Skin Ageing: A Review. International Journal of Cosmetic Science, 30, 87-95. https://doi.org/10.1111/j.1468-2494.2007.00415.x
[2]
Krutmann, J., Schikowski, T., Morita, A. and Berneburg, M. (2021) Environmentally-Induced (Extrinsic) Skin Aging: Exposomal Factors and Underlying Mechanisms. Journal of Investigative Dermatology, 141, 1096-1103. https://doi.org/10.1016/j.jid.2020.12.011
[3]
Araviiskaia, E., Berardesca, E., Bieber, T., Gontijo, G., Sanchez Viera, M., Marrot, L., et al. (2019) The Impact of Airborne Pollution on Skin. Journal of the European Academy of Dermatology and Venereology, 33, 1496-1505. https://doi.org/10.1111/jdv.15583
[4]
Baudouin, C., Charveron, M., Tarroux, R. and Gall, Y. (2002) Environmental Pollutants and Skin Cancer. Cell Biology and Toxicology, 18, 341-348. https://doi.org/10.1023/a:1019540316060
[5]
Kligman, A.M. (1969) Early Destructive Effect of Sunlight on Human Skin. JAMA: The Journal of the American Medical Association, 210, 2377-2380. https://doi.org/10.1001/jama.1969.03160390039008
[6]
Krutmann, J., Bouloc, A., Sore, G., Bernard, B.A. and Passeron, T. (2017) The Skin Aging Exposome. Journal of Dermatological Science, 85, 152-161. https://doi.org/10.1016/j.jdermsci.2016.09.015
[7]
Vierkötter, A., Schikowski, T., Ranft, U., Sugiri, D., Matsui, M., Krämer, U., et al. (2010) Airborne Particle Exposure and Extrinsic Skin Aging. Journal of Investigative Dermatology, 130, 2719-2726. https://doi.org/10.1038/jid.2010.204
[8]
Abolhasani, R., Araghi, F., Tabary, M., Aryannejad, A., Mashinchi, B. and Robati, R.M. (2021) The Impact of Air Pollution on Skin and Related Disorders: A Comprehensive Review. Dermatologic Therapy, 34, e14840. https://doi.org/10.1111/dth.14840
[9]
Richter, H. and Howard, J.B. (2000) Formation of Polycyclic Aromatic Hydrocarbons and Their Growth to Soot—A Review of Chemical Reaction Pathways. Progress in Energy and Combustion Science, 26, 565-608. https://doi.org/10.1016/s0360-1285(00)00009-5
[10]
Perera, F. (1981) Carcinogenicity of Airborne Fine Particulate Benzo(a)pyrene: An Appraisal of the Evidence and the Need for Control. Environmental Health Perspectives, 42, 163-185. https://doi.org/10.1289/ehp.8142163
[11]
Krutmann, J., Liu, W., Li, L., Pan, X., Crawford, M., Sore, G., et al. (2014) Pollution and Skin: From Epidemiological and Mechanistic Studies to Clinical Implications. Journal of Dermatological Science, 76, 163-168. https://doi.org/10.1016/j.jdermsci.2014.08.008
[12]
Fitoussi, R., Faure, M., Beauchef, G. and Achard, S. (2022) Human Skin Responses to Environmental Pollutants: A Review of Current Scientific Models. Environmental Pollution, 306, Article ID: 119316. https://doi.org/10.1016/j.envpol.2022.119316
[13]
Patatian, A., Delestre-Delacour, C., Percoco, G., Ramdani, Y., Di Giovanni, M., Peno-Mazzarino, L., et al. (2021) Skin Biological Responses to Urban Pollution in an ex Vivo Model. Toxicology Letters, 348, 85-96. https://doi.org/10.1016/j.toxlet.2021.05.003
[14]
Wang, S., Sheng, Y., Feng, M., Leszczynski, J., Wang, L., Tachikawa, H., et al. (2007) Light‐Induced Cytotoxicity of 16 Polycyclic Aromatic Hydrocarbons on the US EPA Priority Pollutant List in Human Skin Hacat Keratinocytes: Relationship between Phototoxicity and Excited State Properties. Environmental Toxicology, 22, 318-327. https://doi.org/10.1002/tox.20241
[15]
Soeur, J., Belaïdi, J., Chollet, C., Denat, L., Dimitrov, A., Jones, C., et al. (2017) Photo-pollution Stress in Skin: Traces of Pollutants (PAH and Particulate Matter) Impair Redox Homeostasis in Keratinocytes Exposed to Uva1. Journal of Dermatological Science, 86, 162-169. https://doi.org/10.1016/j.jdermsci.2017.01.007
[16]
van Deursen, J.M. (2014) The Role of Senescent Cells in Ageing. Nature, 509, 439-446. https://doi.org/10.1038/nature13193
[17]
Orioli, D. and Dellambra, E. (2018) Epigenetic Regulation of Skin Cells in Natural Aging and Premature Aging Diseases. Cells, 7, Article 268. https://doi.org/10.3390/cells7120268
[18]
Fraga, M.F., Ballestar, E., Paz, M.F., Ropero, S., Setien, F., Ballestar, M.L., et al. (2005) Epigenetic Differences Arise during the Lifetime of Monozygotic Twins. Proceedings of the National Academy of Sciences, 102, 10604-10609. https://doi.org/10.1073/pnas.0500398102
[19]
Fraga, M.F. and Esteller, M. (2007) Epigenetics and Aging: The Targets and the Marks. Trends in Genetics, 23, 413-418. https://doi.org/10.1016/j.tig.2007.05.008
[20]
Kane, A.E. and Sinclair, D.A. (2019) Epigenetic Changes during Aging and Their Reprogramming Potential. Critical Reviews in Biochemistry and Molecular Biology, 54, 61-83. https://doi.org/10.1080/10409238.2019.1570075
[21]
Dhar, P., Moodithaya, S.S. and Patil, P. (2022) Epigenetic Alterations—The Silent Indicator for Early Aging and Age‐Associated Health‐Risks. Aging Medicine, 5, 287-293. https://doi.org/10.1002/agm2.12236
[22]
Lee, Y., Shin, M.H., Kim, M., Kim, Y.K., Shin, H.S., Lee, D.H., et al. (2021) Increased Histone Acetylation and Decreased Expression of Specific Histone Deacetylases in Ultraviolet-Irradiated and Intrinsically Aged Human Skin in Vivo. International Journal of Molecular Sciences, 22, Article 2032. https://doi.org/10.3390/ijms22042032
[23]
de Oliveira, N.F.P., de Souza, B.F. and de Castro Coêlho, M. (2020) UV Radiation and Its Relation to DNA Methylation in Epidermal Cells: A Review. Epigenomes, 4, Article 23. https://doi.org/10.3390/epigenomes4040023
[24]
Bukowska, B. and Sicińska, P. (2021) Influence of Benzo(a)pyrene on Different Epigenetic Processes. International Journal of Molecular Sciences, 22, Article 13453. https://doi.org/10.3390/ijms222413453
[25]
Wang, Y. and Shi, J. (2021) P53 and DNA Methylation in the Aging Process. Journal of Behavioral and Brain Science, 11, 83-95. https://doi.org/10.4236/jbbs.2021.114007
[26]
O’Donnell, A.H., Edwards, J.R., Rollins, R.A., Kraats, N.D.V., Su, T., Hibshoosh, H.H., et al. (2014) Methylation Abnormalities in Mammary Carcinoma: The Methylation Suicide Hypothesis. Journal of Cancer Therapy, 5, 1311-1324. https://doi.org/10.4236/jct.2014.514131
[27]
Rajarajacholan, U.K. and Riabowol, K. (2015) Aging with ING: A Comparative Study of Different Forms of Stress Induced Premature Senescence. Oncotarget, 6, 34118-34127. https://doi.org/10.18632/oncotarget.5947
[28]
Zhang, J., Zhang, Y., Jiang, J. and Duan, C. (2020) The Crosstalk between Epigenetic Mechanisms and Alternative RNA Processing Regulation. Frontiers in Genetics, 11, Article 998. https://doi.org/10.3389/fgene.2020.00998
[29]
Fayyad-Kazan, M., Kobaisi, F., Nasrallah, A., Matarrese, P., Fitoussi, R., Bourgoin-Voillard, S., et al. (2023) Effect of Ultraviolet Radiation and Benzo[a]pyrene Co-Exposure on Skin Biology: Autophagy as a Potential Target. International Journal of Molecular Sciences, 24, Article No. 5863. https://doi.org/10.3390/ijms24065863
[30]
Nejaddehbashi, F., Bayati, V., Mashali, L., Hashemitabar, M., Abbaspour, M., Moghimipour, E., et al. (2019) Isolating Human Dermal Fibroblasts Using Serial Explant Culture. Stem Cell Investigation, 6, Article No. 23. https://doi.org/10.21037/sci.2019.08.05
[31]
Valacchi, G., Weber, S.U., Luu, C., Cross, C.E. and Packer, L. (2000) Ozone Potentiates Vitamin E Depletion by Ultraviolet Radiation in the Murine Stratum Corneum. FEBS Letters, 466, 165-168. https://doi.org/10.1016/s0014-5793(99)01787-1
[32]
Liu, C., Chen, R., Sera, F., Vicedo-Cabrera, A.M., Guo, Y., Tong, S., et al. (2023) Interactive Effects of Ambient Fine Particulate Matter and Ozone on Daily Mortality in 372 Cities: Two Stage Time Series Analysis. BMJ, 383, e075203. https://doi.org/10.1136/bmj-2023-075203
[33]
Ferrara, F., Woodby, B., Pecorelli, A., Schiavone, M.L., Pambianchi, E., Messano, N., et al. (2020) Additive Effect of Combined Pollutants to UV Induced Skin Oxinflammation Damage. Evaluating the Protective Topical Application of a Cosmeceutical Mixture Formulation. Redox Biology, 34, Article ID: 101481. https://doi.org/10.1016/j.redox.2020.101481
[34]
Burke, K. and Wei, H. (2009) Synergistic Damage by UVA Radiation and Pollutants. Toxicology and Industrial Health, 25, 219-224. https://doi.org/10.1177/0748233709106067
[35]
Martinez-Fernandez, L., Banyasz, A., Esposito, L., Markovitsi, D. and Improta, R. (2017) UV-Induced Damage to DNA: Effect of Cytosine Methylation on Pyrimidine Dimerization. Signal Transduction and Targeted Therapy, 2, Article No. 17021. https://doi.org/10.1038/sigtrans.2017.21
[36]
Law, P. and Holland, M.L. (2019) DNA Methylation at the Crossroads of Gene and Environment Interactions. Essays in Biochemistry, 63, 717-726. https://doi.org/10.1042/ebc20190031
[37]
Rider, C.F. and Carlsten, C. (2019) Air Pollution and DNA Methylation: Effects of Exposure in Humans. Clinical Epigenetics, 11, Article No. 131. https://doi.org/10.1186/s13148-019-0713-2
[38]
Dhar, G.A., Saha, S., Mitra, P. and Nag Chaudhuri, R. (2021) DNA Methylation and Regulation of Gene Expression: Guardian of Our Health. The Nucleus, 64, 259-270. https://doi.org/10.1007/s13237-021-00367-y
[39]
Poursafa, P., Kamali, Z., Fraszczyk, E., Boezen, H.M., Vaez, A. and Snieder, H. (2022) DNA Methylation: A Potential Mediator between Air Pollution and Metabolic Syndrome. Clinical Epigenetics, 14, Article No. 82. https://doi.org/10.1186/s13148-022-01301-y
[40]
Tilburg, J., Slieker, R.C., Suchiman, H.E.D., Heath, A., Heemst, D.V., Slagboom, P.E., et al. (2020) Repeat UVA Exposure of Human Skin Fibroblasts Induces Both a Transitionary and Recovery DNA Methylation Response. Epigenomics, 12, 563-573. https://doi.org/10.2217/epi-2019-0251
[41]
Prigent, C. and Dimitrov, S. (2003) Phosphorylation of Serine 10 in Histone H3, What for? Journal of Cell Science, 116, 3677-3685. https://doi.org/10.1242/jcs.00735
[42]
Ito, T. (2007) Role of Histone Modification in Chromatin Dynamics. Journal of Biochemistry, 141, 609-614. https://doi.org/10.1093/jb/mvm091
[43]
Dong, Z. and Bode, A.M. (2006) The Role of Histone H3 Phosphorylation (Ser10 and Ser28) in Cell Growth and Cell Transformation. Molecular Carcinogenesis, 45, 416-421. https://doi.org/10.1002/mc.20220
[44]
Yang, S., Valvo, S., Yao, H., Kode, A., Rajendrasozhan, S., Edirisinghe, I., et al. (2008) Ikkα Causes Chromatin Modification on Pro-Inflammatory Genes by Cigarette Smoke in Mouse Lung. American Journal of Respiratory Cell and Molecular Biology, 38, 689-698. https://doi.org/10.1165/rcmb.2007-0379oc
[45]
Sawicka, A. and Seiser, C. (2012) Histone H3 Phosphorylation—A Versatile Chromatin Modification for Different Occasions. Biochimie, 94, 2193-2201. https://doi.org/10.1016/j.biochi.2012.04.018
[46]
Blanco, F.J. and Bernabéu, C. (2012) The Splicing Factor SRSF1 as a Marker for Endothelial Senescence. Frontiers in Physiology, 3, Article 54. https://doi.org/10.3389/fphys.2012.00054
[47]
Das, S. and Krainer, A.R. (2014) Emerging Functions of SRSF1, Splicing Factor and Oncoprotein, in RNA Metabolism and Cancer. Molecular Cancer Research, 12, 1195-1204. https://doi.org/10.1158/1541-7786.mcr-14-0131
[48]
Lim, Y.W., James, D., Huang, J. and Lee, M. (2020) The Emerging Role of the RNA-Binding Protein SFPQ in Neuronal Function and Neurodegeneration. International Journal of Molecular Sciences, 21, Article 7151. https://doi.org/10.3390/ijms21197151
[49]
Guo, P., Chen, S., Li, D., Zhang, J., Luo, J., Zhang, A., et al. (2020) SFPQ Is Involved in Regulating Arsenic-Induced Oxidative Stress by Interacting with the Mirna-Induced Silencing Complexes. Environmental Pollution, 261, Article ID: 114160. https://doi.org/10.1016/j.envpol.2020.114160
[50]
Zhao, C., Zhu, L., Li, R., Wang, H. and Cai, Z. (2019) Omics Approach Reveals Metabolic Disorders Associated with the Cytotoxicity of Airborne Particulate Matter in Human Lung Carcinoma Cells. Environmental Pollution, 246, 45-52. https://doi.org/10.1016/j.envpol.2018.11.108
[51]
Guarino, F., Cicatelli, A., Brundu, G., Improta, G., Triassi, M. and Castiglione, S. (2019) The Use of MSAP Reveals Epigenetic Diversity of the Invasive Clonal Populations of Arundo donax L. PLOS ONE, 14, e0215096. https://doi.org/10.1371/journal.pone.0215096
[52]
Guarino, F., Miranda, A., Castiglione, S. and Cicatelli, A. (2020) Arsenic Phytovolatilization and Epigenetic Modifications in Arundo donax L. Assisted by a PGPR Consortium. Chemosphere, 251, Article ID: 126310. https://doi.org/10.1016/j.chemosphere.2020.126310
[53]
Yiannakopoulou, E.C. (2015) Targeting DNA Methylation with Green Tea Catechins. Pharmacology, 95, 111-116. https://doi.org/10.1159/000375503
[54]
Musial, C., Kuban-Jankowska, A. and Gorska-Ponikowska, M. (2020) Beneficial Properties of Green Tea Catechins. International Journal of Molecular Sciences, 21, Article 1744. https://doi.org/10.3390/ijms21051744
[55]
Fatima, N., Baqri, S.S.R., Bhattacharya, A., Koney, N.K., Husain, K., Abbas, A., et al. (2021) Role of Flavonoids as Epigenetic Modulators in Cancer Prevention and Therapy. Frontiers in Genetics, 12, Article 758733. https://doi.org/10.3389/fgene.2021.758733
[56]
Zuo, Q., Wu, R., Xiao, X., Yang, C., Yang, Y., Wang, C., et al. (2018) The Dietary Flavone Luteolin Epigenetically Activates the Nrf2 Pathway and Blocks Cell Transformation in Human Colorectal Cancer HCT116 Cells. Journal of Cellular Biochemistry, 119, 9573-9582. https://doi.org/10.1002/jcb.27275
[57]
Kang, K.A., Piao, M.J., Hyun, Y.J., Zhen, A.X., Cho, S.J., Ahn, M.J., et al. (2019) Luteolin Promotes Apoptotic Cell Death via Upregulation of Nrf2 Expression by DNA Demethylase and the Interaction of Nrf2 with P53 in Human Colon Cancer Cells. Experimental & Molecular Medicine, 51, 1-14. https://doi.org/10.1038/s12276-019-0238-y
[58]
Pramodh, S., Raina, R., Hussain, A., Bagabir, S.A., Haque, S., Raza, S.T., et al. (2022) Luteolin Causes 5’CpG Demethylation of the Promoters of TSGs and Modulates the Aberrant Histone Modifications, Restoring the Expression of TSGs in Human Cancer Cells. International Journal of Molecular Sciences, 23, Article 4067. https://doi.org/10.3390/ijms23074067
