Abstract
Ultraviolet (UV) radiation is one of the main environmental factors leading to oxidative stress and accelerated skin aging. AEDG peptide, a regulator of pineal gland functions, has demonstrated geroprotective and antioxidant effects in in vivo and in vitro studies. The aim of this research was to evaluate the effect of AEDG peptide on the expression of genes encoding enzymes of the antioxidant system (NQO1, SOD1, CATALASE, and TRXR) in human skin fibroblasts in a model of accelerated aging induced by UV radiation. The expression of SOD1 and TXNRD1 genes during UV-induced aging of dermal fibroblasts increases by 2 and 1.7 times, respectively. This can be considered as a defense mechanism against oxidative stress caused by UV radiation. Photoaging does not influence the expression of the NQO1 and CATALASE genes in the culture of skin fibroblasts. AEDG peptide promotes the expression of the SOD-1, NQO1, and CATALASE genes in dermal fibroblasts exposed to UV radiation by 2.7, 2.6, and 3.2 times, respectively. AEDG peptide can stimulate the expression of these genes via the Keap1/Nrf2 signaling pathway. AEDG peptide might be potentially effective in preventing the accelerated aging of dermal fibroblasts.
Similar content being viewed by others
REFERENCES
Fridman, N.V., Lin’kova, N.S., Boiko, L.V., and Kakheli, M.A., Effects of peptide bioregulators on structural and functional peculiarities of facial skin in elderly women, Mol. Med., 2021, no. 4, pp. 42–46.
Cavinato, M., Koziel, R., Romani, N., et al., UVB-induced senescence of human dermal fibroblasts involves impairment of proteasome and enhanced autophagic activity, J. Gerontol. A Biol. Sci. Med. Sci., 2017, vol. 72, no. 5, pp. 632–639.
Choi, J.W., Lee, J., and Park, Y.I., 7,8-Dihydroxyflavone attenuates TNF-α-induced skin aging in Hs68 human dermal fibroblast cells via down-regulation of the MAPKs/Akt signaling pathways, Biomed. Pharmacother., 2017, vol. 95, pp. 1580–1587.
De Tollenaere, M., Meunier, M., Scandolera, A., et al., Well-aging: a new strategy for skin homeostasis under multi-stressed conditions, J. Cosmet. Dermatol., 2020, vol. 19, no. 2, pp. 444–455.
Gęgotek, A., Ambrożewicz, E., Jastrząb, A., et al., Rutin and ascorbic acid cooperation in antioxidant and antiapoptotic effect on human skin keratinocytes and fibroblasts exposed to UVA and UVB radiation, Arch. Dermatol. Res., 2019, vol. 311, no. 3, pp. 203–219.
Gravitz, L., Skin, Nature, 2018, vol. 563, no. 7732, p. 83. https://doi.org/10.1038/d41586-018-07428-4
Gromkowska-Kępka, K.J., PuścionJakubik, A., Markiewicz-Żukowska, R., and Socha, K., The impact of ultraviolet radiation on skin photoaging—review of in vitro studies, J. Cosmet. Dermatol., 2021. https://doi.org/10.1111/jocd.14033
Gu, Y., Han, J., Jiang, C., and Zhang, Y., Biomarkers, oxidative stress and autophagy in skin aging, Ageing Res. Rev., 2020, vol. 59, p. 101036. https://doi.org/10.1016/j.arr.2020.101036
Il’ina, T.N., Vinogradova, I.A., Iliukha, V.A., et al., The influences of geroprotectors on age-related changes of antioxidant system in rats liver under different light condition, Adv. Gerontol., 2008, vol. 21, no. 3, pp. 386–393.
Ivko, O.M., Linkova, N.S., Ilina, A.R., et al., AEDG peptide regulates human circadian rhythms genes expression during pineal gland accelerated aging, Adv. Gerontol., 2020, vol. 33, no. 3, pp. 429–435.
Kammeyer, A. and Luiten, R.M., Oxidation events and skin aging, Ageing Res. Rev., 2015, vol. 21, pp. 16–29.
Khavinson, V.Kh., Bondarev, I.E., and Butyugov, A.A., Epithalon peptide induces telomerase activity and telomere elongation in human somatic cells, Bull. Exp. Biol. Med., 2003, vol. 135, no. 6, pp. 590–592.
Khavinson, V.Kh., Lezhava, T.A., Monaselidze, J.R., et al., Peptide epitalon activates chromatin at the old age, Neuro Endocrinol. Lett., 2003, vol. 24, no. 5, pp. 329–333.
Khavinson, V.Kh., Linkova, N.S., and Tarnovskaya, S.I., Short peptides regulate gene expression, Bull. Exp. Biol. Med., 2016, vol. 162, no. 2, pp. 288–292.
Khavinson, V.Kh., Pendina, A.A., Efimova, O.A., et al., Effect of peptide AEDG on telomere length and mitotic index of PHA-stimulated human blood lymphocytes, Bull. Exp. Biol. Med., 2019, vol. 168, no. 1, pp. 141–144.
Khavinson, V., Diomede, F., Mironova, E., et al., AEDG peptide (epitalon) stimulates gene expression and protein synthesis during neurogenesis: possible epigenetic mechanism, Molecules, 2020, vol. 25, no. 3, p. 609. https://doi.org/10.3390/molecules25030609
Kim, J., Toda, T., Watanabe, K., et al., Syringaresinol reverses age-related skin atrophy by suppressing FoxO3a-mediated matrix metalloproteinase-2 activation in copper/zinc superoxide dismutase-deficient mice, J. Invest. Dermatol., 2019, vol. 139, no. 3, pp. 648–655.
Kozina, L.S., Arutjunyan, A.V., and Khavinson, V.Kh., Antioxidant properties of geroprotective peptides of the pineal gland, Arch. Gerontol. Geriatr., 2007, vol. 44, suppl. 1, pp. 213–216.
Lephart, E.D., Skin aging and oxidative stress: equol’s anti-aging effects via biochemical and molecular mechanisms, Ageing Res. Rev., 2016, vol. 31, pp. 36–54.
Letsiou, S., Bakea, A., Goff, G.L., et al., Marine fungus Aspergillus chevalieri TM2-S6 extract protects skin fibroblasts from oxidative stress, Mar. Drugs, 2020, vol. 18, no. 9, p. 460. https://doi.org/10.3390/md18090460
Li, Z., Galli, U., Becker, L.E., et al., Sulforaphane protects hearts from early injury after experimental transplantation, Ann. Transplant., 2013, vol. 18, pp. 558–566.
Lone, A.N., Malik, A.T., Naikoo, H.S., Raghu, R.S., and Tasduq, S.A., Trigonelline, a naturally occurring alkaloidal agent protects ultraviolet-B (UV-B) irradiation induced apoptotic cell death in human skin fibroblasts via attenuation of oxidative stress, restoration of cellular calcium homeostasis and prevention of endoplasmic reticulum (ER) stress, J. Photochem. Photobiol., vol. 202, p. 111720. https://doi.org/10.1016/j.jphotobiol.2019.111720
Qian, X., Asad, S.B., Li, J., et al., Link between cardiac function and the antioxidative defense mechanism in aged rats, Biochem. Biophys. Res. Commun., 2019, vol. 513, no. 4, pp. 1100–1105.
Sannasimuthu, A., Kumaresan, V., Anilkumar, S., et al., Design and characterization of a novel Arthrospira platensis glutathione oxido-reductase-derived antioxidant peptide GM15 and its potent anti-cancer activity via caspase-9 mediated apoptosis in oral cancer cells, Free Radical Biol. Med., 2019, vol. 135, pp. 198–209.
Shin, M.H., Lee, S.R., Kim, M.K., et al., Activation of peroxisome proliferator-activated receptor alpha improves aged and UV-irradiated skin by catalase induction, PLoS One, 2016, vol. 11, no. 9. e0162628. https://doi.org/10.1371/journal.pone.0162628
Toshihiro, F., Teruyuki, D., Zeshaan, N.M., et al., Age-associated intracellular superoxide dismutase deficiency potentiates dermal fibroblast dysfunction during wound healing, Exp. Dermatol., 2019, vol. 28, no. 4, pp. 485–492.
Xie, L., Pandey, R., Xu, B., et al., Genomic and proteomic profiling of oxidative stress response in human diploid fibroblasts, Biogerontology, 2009, vol. 10, no. 2, pp. 125–151.
Zhang, J.A., Yin, Z., Ma, L.W., et al., The protective effect of baicalin against UVB irradiation induced photoaging: an in vitro and in vivo study, PLoS One, 2014, vol. 9, no. 6. e99703. https://doi.org/10.1371/journal.pone.0099703
Zhong, G., He, Y., Wan, F., et al., Effects of long-term exposure to copper on the KEAP1/NRF2 signaling pathway and MSR-related redox status in the kidneys of rats, Biol. Trace Elem. Res., 2021. https://doi.org/10.1007/s12011-020-02557-2
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interests. The authors declare that they have no conflict of interest.
Statement of compliance with standards of research involving humans as subjects. Patient signed an informed consent. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants involved in the study.
Additional information
Translated by E. Sherstyuk
Rights and permissions
About this article
Cite this article
Gutop, E.O., Linkova, N.S., Kozhevnikova, E.O. et al. AEDG Peptide Prevents Oxidative Stress in the Model of Induced Aging of Skin Fibroblasts. Adv Gerontol 12, 143–148 (2022). https://doi.org/10.1134/S2079057022020096
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S2079057022020096