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

Biomolecules & Therapeutics 2021년 29권 1호 p.90 ~ 97
Piao Mei Jing, 김기천, 강경아, Fernando Pincha Devage Sameera Madushan, Herath Herath Mudiyanselage Udari Lakmini, 현진원,
소속 상세정보
 ( Piao Mei Jing ) - Jeju National University School of Medicine Department of Biochemistry
김기천 ( Kim Ki-Cheon ) - Korea Institute of Toxicology National Center for Efficacy Evaluation of Respiratory Disease Product
강경아 ( Kang Kyoung-Ah ) - Jeju National University School of Medicine Department of Biochemistry
 ( Fernando Pincha Devage Sameera Madushan ) - Jeju National University School of Medicine Department of Biochemistry
 ( Herath Herath Mudiyanselage Udari Lakmini ) - Jeju National University School of Medicine Department of Biochemistry
현진원 ( Hyun Jin-Won ) - Jeju National University School of Medicine Department of Biochemistry

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.

키워드

Phloroglucinol; Ultraviolet B; 8-oxoguanine DNA glycosylase 1; NF-E2-related factor 2; Protein kinase B; Extracellular signal-regulated kinase

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