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http://dx.doi.org/10.4062/biomolther.2020.059

Phloroglucinol Attenuates Ultraviolet B-Induced 8-Oxoguanine Formation in Human HaCaT Keratinocytes through Akt and Erk-Mediated Nrf2/Ogg1 Signaling Pathways  

Piao, Mei Jing (Department of Biochemistry, College of Medicine, Jeju National University and Jeju Research Center for Natural Medicine)
Kim, Ki Cheon (National Center for Efficacy Evaluation of Respiratory Disease Product, Korea Institute of Toxicology)
Kang, Kyoung Ah (Department of Biochemistry, College of Medicine, Jeju National University and Jeju Research Center for Natural Medicine)
Fernando, Pincha Devage Sameera Madushan (Department of Biochemistry, College of Medicine, Jeju National University and Jeju Research Center for Natural Medicine)
Herath, Herath Mudiyanselage Udari Lakmini (Department of Biochemistry, College of Medicine, Jeju National University and Jeju Research Center for Natural Medicine)
Hyun, Jin Won (Department of Biochemistry, College of Medicine, Jeju National University and Jeju Research Center for Natural Medicine)
Publication Information
Biomolecules & Therapeutics / v.29, no.1, 2021 , pp. 90-97 More about this Journal
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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