Biomolecules & Therapeutics  https://doi.org/10.4062/biomolther.2020.059
Phloroglucinol Attenuates Ultraviolet B-Induced 8-Oxoguanine Formation in Human HaCaT Keratinocytes through Akt and ErkMediated Nrf2/Ogg1 Signaling Pathways
Mei Jing Piao1,†, Ki Cheon Kim2,†, Kyoung Ah Kang1, Pincha Devage Sameera Madushan Fernando1, Herath Mudiyanselage Udari Lakmini Herath1 and Jin Won Hyun1,*
1Department of Biochemistry, College of Medicine, Jeju National University and Jeju Research Center for Natural Medicine, Jeju 63243,
2National Center for Efficacy Evaluation of Respiratory Disease Product, Korea Institute of Toxicology, Jeongeup 56212, Republic of Korea
E-mail: jinwonh@jejunu.ac.kr
Tel: +82-64-754-3838, Fax: +82-64-702-2687
The first two authors contributed equally to this work
Received: April 13, 2020; Revised: May 15, 2020; Accepted: May 19, 2020; Published online: June 26, 2020.
© The Korean Society of Applied Pharmacology. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Ultraviolet B (UVB) radiation causes DNA base modifications. One of these changes leads to the generation of 8-oxoguanine (8- oxoG) due to oxidative stress. In human skin, this modification may induce sunburn, inflammation, and aging and may ultimately result in cancer. We investigated whether phloroglucinol (1,3,5-trihydroxybenzene), by enhancing the expression and activity of 8-oxoG DNA glycosylase 1 (Ogg1), had an effect on the capacity of UVB-exposed human HaCaT keratinocytes to repair oxidative DNA damage. Here, the effects of phloroglucinol were investigated using a luciferase activity assay, reverse transcription-polymerase chain reactions, western blot analysis, and a chromatin immunoprecipitation assay. Phloroglucinol restored Ogg1 activity and decreased the formation of 8-oxoG in UVB-exposed cells. Moreover, phloroglucinol increased Ogg1 transcription and protein expression, counteracting the UVB-induced reduction in Ogg1 levels. Phloroglucinol also enhanced the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) as well as Nrf2 binding to an antioxidant response element located in the Ogg1 gene promoter. UVB exposure inhibited the phosphorylation of protein kinase B (PKB or Akt) and extracellular signal-regulated kinase (Erk), two major enzymes involved in cell protection against oxidative stress, regulating the activity of Nrf2. Akt and Erk phosphorylation was restored by phloroglucinol in the UVB-exposed keratinocytes. These results indicated that phloroglucinol attenuated UVB-induced 8-oxoG formation in keratinocytes via an Akt/Erk-dependent, Nrf2/Ogg1-mediated signaling pathway.
Keywords: Phloroglucinol, Ultraviolet B, 8-oxoguanine DNA glycosylase 1, NF-E2-related factor 2, Protein kinase B, Extracellular signal-regulated kinase


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