Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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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)
  • Received : 2020.04.13
  • Accepted : 2020.05.19
  • Published : 2021.01.01
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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

References

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