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Cited by 77Sirtuins and Resveratrol in MedicineRetinal Diseases and TreatmentsOcular and Laser Science Research

Protective Effects of Resveratrol against UVA-Induced Damage in ARPE19 Cells

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Chan, Chi-Ming, Huang, Cheng-Hua, Li, Hsin-Ju, Hsiao, Chien-Yu, Su, Ching-Chieh, Lee, Pei-Lan, Hung, Chi-Feng·2015·International Journal of Molecular Sciences
DOI 10.3390/ijms16035789PMC PMC4394506
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Abstract

Ultraviolet radiation, especially UVA, can penetrate the lens, reach the retina, and induce oxidative stress to retinal pigment epithelial (RPE) cells. Even though it is weakly absorbed by protein and DNA, it may trigger the production of reactive oxygen species (ROS) and generate oxidative injury; oxidative injury to the retinal pigment epithelium has been implicated to play a contributory role in age-related macular degeneration (AMD). Studies showed that resveratrol, an abundant and active component of red grapes, can protect several cell types from oxidative stress. In this study, adult RPE cells being treated with different concentrations of resveratrol were used to evaluate the protective effect of resveratrol on RPE cells against UVA-induced damage. Cell viability assay showed that resveratrol reduced the UVA-induced decrease in RPE cell viability. Through flow cytometry analysis, we found that the generation of intracellular H2O2 induced by UVA irradiation in RPE cells could be suppressed by resveratrol in a concentration-dependent manner. Results of Western blot analysis demonstrated that resveratrol lowered the activation of UVA-induced extracellular signal-regulated kinase, c-jun-NH2 terminal kinase and p38 kinase in RPE cells. In addition, there was also a reduction in UVA-induced cyclooxygenase-2 (COX-2) expression in RPE cells pretreated with resveratrol. Our observations suggest that resveratrol is effective in preventing RPE cells from being damaged by UVA radiation, and is worth considering for further development as a chemoprotective agent for the prevention of early AMD.

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  • Oxidative stress activates MAPK components ERK, JNK, and p38, which contribute to RPE cell apoptosis, inflammatory responses, and pathological angiogenesis.

    “Oxidative stress, a key driver of AMD, activates MAPK components-including ERK, JNK, and p38-which contribute to retinal pigment epithelium (RPE) cell apoptosis, inflammatory responses, and pathological angiogenesis 16,17,37,38 .”

    From rAAV-mediated Multi-miRNA Delivery Targeting MAPK Pathway Suppresses Laser-induced Choroidal Neovascularization in Mice (2026) · cites this paper as [37]

    The Results (§2.4) show UVA-induced activation of ERK, JNK, and p38 in ARPE19 cells. The Discussion links JNK and p38 to apoptosis, ERK1/2 to VEGF upregulation that may relate to neovascularization, and MAPK activation to COX-2 expression. It does not establish that all three components contribute to each listed outcome; it also describes ERK activation as a possible survival pathway against UV-induced cell death. (LLM, conf=0.86)

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  1. [1]Murthy R.K. Ravi K. Balaiya S. Brar V.S. Chalam K.V. Lutein protects retinal pigment epithelium from cytotoxic oxidative stress Cutan. Ocul. Toxicol. 2014 33 132 137 10.3109/15569527.2013.812108 23862688 · DOI
  2. [2]Glickman R.D. Ultraviolet phototoxicity to the retina Eye Contact Lens 2011 37 196 205 10.1097/ICL.0b013e31821e45a9 21646980 · DOI
  3. [3]Roduit R. Schorderet D.F. MAP kinase pathways in UV-induced apoptosis of retinal pigment epithelium ARPE19 cells Apoptosis 2008 13 343 353 10.1007/s10495-008-0179-8 18253836 · DOI · Paper page
  4. [4]Roberts J.E. Ultraviolet radiation as a risk factor for cataract and macular degeneration Eye Contact Lens 2011 37 246 249 10.1097/ICL.0b013e31821cbcc9 21617534 · DOI
  5. [5]Lim L.S. Mitchell P. Seddon J.M. Holz F.G. Wong T.Y. Age-related macular degeneration Lancet 2012 379 1728 1738 10.1016/S0140-6736(12)60282-7 22559899 · DOI
  6. [6]Bressler N.M. Age-related macular degeneration is the leading cause of blindness JAMA 2004 291 1900 1901 10.1001/jama.291.15.1900 15108691 · DOI
  7. [7]Chan C.M. Huang J.H. Lin H.H. Chiang H.S. Chen B.H. Hong J.Y. Hung C.F. Protective effects of (−)-epigallocatechin gallate on UVA-induced damage in ARPE19 cells Mol. Vis. 2008 14 2528 2534 19119326 PMC2612705
  8. [8]Yao J. Bi H.E. Sheng Y. Cheng L.B. Wendu R.L. Wang C.H. Cao G.F. Jiang Q. Ultraviolet (UV) and hydrogen peroxide activate ceramide-ER stress-AMPK signaling axis to promote retinal pigment epithelium (RPE) cell apoptosis Int. J. Mol. Sci. 2013 14 10355 10368 10.3390/ijms140510355 23685869 PMC3676843 · DOI
  9. [9]Artigas J.M. Felipe A. Navea A. Artigas C. Garcia-Domene M.C. Spectral transmittance of intraocular lenses under natural and artificial illumination: criteria analysis for choosing a suitable filter Ophthalmology 2011 118 3 8 10.1016/j.ophtha.2010.06.023 20801517 · DOI
  10. [10]Brockmann C. Schulz M. Laube T. Transmittance characteristics of ultraviolet and blue-light-filtering intraocular lenses J. Cataract Refract. Surg. 2008 34 1161 1166 10.1016/j.jcrs.2008.03.039 18571086 · DOI
  11. [11]He S. Yan X. From resveratrol to its derivatives: New sources of natural antioxidant Curr. Med. Chem. 2013 20 1005 1017 23210785
  12. [12]Suzuki Y. Ito S. Sasaki R. Asahi M. Ishida Y. Resveratrol suppresses cell proliferation via inhibition of STAT3 phosphorylation and Mcl-1 and cIAP-2 expression in HTLV-1-infected T cells Leuk. Res. 2013 37 1674 1679 10.1016/j.leukres.2013.09.010 24090995 · DOI
  13. [13]Svajger U. Jeras M. Anti-inflammatory effects of resveratrol and its potential use in therapy of immune-mediated diseases Int. Rev. Immunol. 2012 31 202 222 10.3109/08830185.2012.665108 22587021 · DOI
  14. [14]Ogas T. Kondratyuk T.P. Pezzuto J.M. Resveratrol analogs: Promising chemopreventive agents Ann. N. Y. Acad. Sci. 2013 1290 21 29 10.1111/nyas.12196 23855462 · DOI
  15. [15]Raederstorff D. Kunz I. Schwager J. Resveratrol, from experimental data to nutritional evidence: The emergence of a new food ingredient Ann. N. Y. Acad. Sci. 2013 1290 136 141 10.1111/nyas.12147 23855476 · DOI
  16. [16]Singh C.K. George J. Ahmad N. Resveratrol-based combinatorial strategies for cancer management Ann. N. Y. Acad. Sci. 2013 1290 113 121 10.1111/nyas.12160 23855473 PMC3713511 · DOI
  17. [17]Pintea A. Rugina D. Pop R. Bunea A. Socaciu C. Diehl H.A. Antioxidant effect of trans-resveratrol in cultured human retinal pigment epithelial cells J. Ocul. Pharmacol. Ther. 2011 27 315 321 10.1089/jop.2010.0144 21663493 · DOI
  18. [18]Sheu S.J. Liu N.C. Ou C.C. Bee Y.S. Chen S.C. Lin H.C. Chan J.Y. Resveratrol stimulates mitochondrial bioenergetics to protect retinal pigment epithelial cells from oxidative damage Investig. Ophthalmol. Vis. Sci. 2013 54 6426 6438 10.1167/iovs.13-12024 24008411 · DOI
  19. [19]Chao S.C. Hu D.N. Yang P.Y. Lin C.Y. Nien C.W. Yang S.F. Roberts J.E. Ultraviolet-A irradiation upregulated urokinase-type plasminogen activator in pterygium fibroblasts through ERK and JNK pathways Investig. Ophthalmol. Vis. Sci. 2013 54 999 1007 10.1167/iovs.12-10469 23322578 · DOI
  20. [20]Mikulski D. Gorniak R. Molski M. A theoretical study of the structure-radical scavenging activity of trans-resveratrol analogues and cis-resveratrol in gas phase and water environment Eur. J. Med. Chem. 2010 45 1015 1027 10.1016/j.ejmech.2009.11.044 20004046 · DOI
  21. [21]King R.E. Kent K.D. Bomser J.A. Resveratrol reduces oxidation and proliferation of human retinal pigment epithelial cells via extracellular signal-regulated kinase inhibition Chem. Biol. Interact. 2005 151 143 149 10.1016/j.cbi.2004.11.003 15698585 · DOI
  22. [22]Sheu S.J. Bee Y.S. Chen C.H. Resveratrol and large-conductance calcium-activated potassium channels in the protection of human retinal pigment epithelial cells J. Ocul. Pharmacol. Ther. 2008 24 551 555 10.1089/jop.2008.0013 19049310 · DOI
  23. [23]Chan C.M. Chang H.H. Wang V.C. Huang C.L. Hung C.F. Inhibitory effects of resveratrol on PDGF-BB-induced retinal pigment epithelial cell migration via PDGFRβ, PI3K/Akt and MAPK pathways PLoS One 2013 8 e56819 10.1371/journal.pone.0056819 23457620 PMC3572951 · DOI
  24. [24]Sheu S.J. Wu T.T. Resveratrol protects against ultraviolet A-mediated inhibition of the phagocytic function of human retinal pigment epithelial cells via large-conductance calcium-activated potassium channels Kaohsiung J. Med. Sci. 2009 25 381 388 10.1016/S1607-551X(09)70531-5 19605330 PMC11917912 · DOI
  25. [26]Baumler W. Regensburger J. Knak A. Felgentrager A. Maisch T. UVA and endogenous photosensitizers—The detection of singlet oxygen by its luminescence Photochem. Photobiol. Sci. 2012 11 107 117 10.1039/C1PP05142C 21986813 · DOI
  26. [27]Ho T.C. Yang Y.C. Cheng H.C. Wu A.C. Chen S.L. Chen H.K. Tsao Y.P. Activation of mitogen-activated protein kinases is essential for hydrogen peroxide -induced apoptosis in retinal pigment epithelial cells Apoptosis 2006 11 1899 1908 10.1007/s10495-006-9403-6 16927023 · DOI · Paper page
  27. [28]Zhong J.L. Yang L. Lu F. Xiao H. Xu R. Wang L. Zhu F. Zhang Y. UVA, UVB and UVC induce differential response signaling pathways converged on the eIF2α phosphorylation Photochem. Photobiol. 2011 87 1092 1104 10.1111/j.1751-1097.2011.00963.x 21707633 · DOI
  28. [29]Wu N.L. Fang J.Y. Chen M. Wu C.J. Huang C.C. Hung C.F. Chrysin protects epidermal keratinocytes from UVA- and UVB-induced damage J. Agric. Food Chem. 2011 59 8391 8400 10.1021/jf200931t 21699266 · DOI
  29. [30]Tsoyi K. Park H.B. Kim Y.M. Chung J.I. Shin S.C. Lee W.S. Seo H.G. Lee J.H. Chang K.C. Kim H.J. Anthocyanins from black soybean seed coats inhibit UVB-induced inflammatory cylooxygenase-2 gene expression and PGE2 production through regulation of the nuclear factor-κB and phosphatidylinositol 3-kinase/Akt pathway J. Agric. Food Chem. 2008 56 8969 8974 10.1021/jf801345c 18778065 · DOI
  30. [31]Lim do Y. Lee M.H. Shin S.H. Chen H. Ryu J. Shan L. Li H. Bode A.M. Zhang W.D. Dong Z. (+)-2-(1-Hydroxyl-4-oxocyclohexyl) ethyl caffeate suppresses solar UV-induced skin carcinogenesis by targeting PI3K, ERK1/2, and p38 Cancer Prev. Res. (Phila.) 2014 7 856 865 10.1158/1940-6207.CAPR-13-0286 24845061 PMC4125463 · DOI
  31. [32]Klettner A. Oxidative stress induced cellular signaling in RPE cells Front. Biosci. (Sch. Ed.) 2012 4 392 411 10.2741/S275 22202067 · DOI · Paper page
  32. [33]Quyen B.T. Choi H.K. Kang K.W. Pin1 is required for ultraviolet A-stimulated cyclooxygenase-2 induction in mouse epidermal cells Cancer Lett. 2013 335 31 40 10.1016/j.canlet.2013.01.047 23380442 · DOI
  33. [34]Kamijo M. Nishiyama C. Takagi A. Nakano N. Hara M. Ikeda S. Okumura K. Ogawa H. Cyclooxygenase-2 inhibition restores ultraviolet B-induced downregulation of ATP2A2/SERCA2 in keratinocytes: Possible therapeutic approach of cyclooxygenase-2 inhibition for treatment of Darier disease Br. J. Dermatol. 2012 166 1017 1022 10.1111/j.1365-2133.2011.10789.x 22413864 · DOI
  34. [35]Li J. Mansmann U.R. Modeling of non-steroidal anti-inflammatory drug effect within signaling pathways and miRNA-regulation pathways PLoS One 2013 8 e72477 10.1371/journal.pone.0072477 23967306 PMC3743815 · DOI
  35. [36]Salvado M.D. Alfranca A. Haeggstrom J.Z. Redondo J.M. Prostanoids in tumor angiogenesis: Therapeutic intervention beyond COX-2 Trends Mol. Med. 2012 18 233 243 10.1016/j.molmed.2012.02.002 22425675 · DOI
  36. [37]Yanni S.E. Barnett J.M. Clark M.L. Penn J.S. The role of PGE2 receptor EP4 in pathologic ocular angiogenesis Investig. Ophthalmol. Vis. Sci. 2009 50 5479 5486 10.1167/iovs.09-3652 19494202 PMC4071769 · DOI
  37. [38]Hu W. Criswell M.H. Ottlecz A. Cornell T.L. Danis R.P. Lambrou G.N. Ciulla T.A. Oral administration of lumiracoxib reduces choroidal neovascular membrane development in the rat laser-trauma model Retina 2005 25 1054 64 10.1097/00006982-200512000-00015 16340537 · DOI
  38. [39]Takahashi H. Yanagi Y. Tamaki Y. Uchida S. Muranaka K. COX-2-selective inhibitor, etodolac, suppresses choroidal neovascularization in a mice model Biochem. Biophys. Res. Commun. 2004 325 461 466 10.1016/j.bbrc.2004.10.054 15530415 · DOI
  39. [40]Rezaei K.A. Toma H.S. Cai J. Penn J.S. Sternberg P. Kim S.J. Reduced choroidal neovascular membrane formation in cyclooxygenase-2 null mice Investig. Ophthalmol. Vis. Sci. 2011 52 701 707 10.1167/iovs.10-6319 20881304 PMC3053102 · DOI
  40. [41]Maloney S.C. Fernandes B.F. Castiglione E. Antecka E. Martins C. Marshall J.C. di Cesare S. Logan P. Burnier M.N. Jr. Expression of cyclooxygenase-2 in choroidal neovascular membranes from age-related macular degeneration patients Retina 2009 29 176 180 10.1097/IAE.0b013e3181884fa6 18827739 · DOI
  41. [42]Mancini A.D. Di Battista J.A. The cardinal role of the phospholipase A2/cyclooxygenase-2/prostaglandin E synthase/prostaglandin E2 (PCPP) axis in inflammostasis Inflamm. Res. 2011 60 1083 1092 10.1007/s00011-011-0385-7 21964881 · DOI

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Authors
Chan, C.-M., Huang, C.-H., Li, H.-J., Hsiao, C.-Y., Su, C.-C., Lee, P.-L., & Hung, C.-F.
Affiliations
  • Fu Jen Catholic University (TW)
  • Chang Gung University of Science and Technology (TW)
  • Boston University (US)
Corresponding author
Hung, Chi-Feng
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2015-03-12
Volume
16
Issue
3
Pages
5789-5802
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms16035789
PMC
PMC4394506
OpenAlex
W2071889856
Cited by
77
References
1
Citations by year
2026: 5 · 2025: 8 · 2024: 6 · 2023: 6 · 2022: 6 · 2021: 10 · 2020: 7 · 2019: 6 · 2018: 9 · 2017: 4 · 2016: 9 · 2015: 1
FWCI
3.84
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Cathay General Hospital
  • Cardinal Tien Hospital
Topics
  • Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
  • Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
  • Health Sciences › Medicine › Ophthalmology › Ocular and Laser Science Research
Keywords
resveratrol, UVA, retinal pigment epithelium, ARPE-19 cells, oxidative stress, age-related macular degeneration, hydrogen peroxide, reactive oxygen species, ERK, JNK, p38 MAPK, cyclooxygenase-2, cell viability, chemoprotection
MeSH terms
Resveratrol, Cell Line, Cell Survival, Humans, Hydrogen Peroxide, Phosphorylation, Radiation-Protective Agents, Stilbenes, Ultraviolet Rays, Oxidative Stress, JNK Mitogen-Activated Protein Kinases, Extracellular Signal-Regulated MAP Kinases, p38 Mitogen-Activated Protein Kinases, Cyclooxygenase 2, Retinal Pigment Epithelium

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