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Mechanisms of Resorcinol Antagonism of Benzo[a]pyrene-Induced Damage to Human Keratinocytes

Biomolecules & Therapeutics 2021년 29권 2호 p.227 ~ 233
이승은, 권기태, Oh Sae-Woong, 박세정, 유은비, 김혜연, 양세영, 박정연, 정우제, 조제율, 이종성,
소속 상세정보
이승은 ( Lee Seung-Eun ) - Sungkyunkwan University College of Biotechnology and Bioengineering Department of Integrative Biotechnology
권기태 ( Kwon Ki-Tae ) - Sungkyunkwan University College of Biotechnology and Bioengineering Department of Integrative Biotechnology
 ( Oh Sae-Woong ) - Sungkyunkwan University College of Biotechnology and Bioengineering Department of Integrative Biotechnology
박세정 ( Park Se-Jung ) - Sungkyunkwan University College of Biotechnology and Bioengineering Department of Integrative Biotechnology
유은비 ( Yu Eun-Bi ) - Sungkyunkwan University College of Biotechnology and Bioengineering Department of Integrative Biotechnology
김혜연 ( Kim Hye-Youn ) - Sungkyunkwan University College of Biotechnology and Bioengineering Department of Integrative Biotechnology
양세영 ( Yang Se-Young ) - Sungkyunkwan University College of Biotechnology and Bioengineering Department of Integrative Biotechnology
박정연 ( Park Jung-Yoen ) - Sungkyunkwan University College of Biotechnology and Bioengineering Department of Integrative Biotechnology
정우제 ( Chung Woo-Jae ) - Sungkyunkwan University College of Biotechnology and Bioengineering Department of Integrative Biotechnology
조제율 ( Cho Jae-Youl ) - Sungkyunkwan University College of Biotechnology and Bioengineering Department of Integrative Biotechnology
이종성 ( Lee Jong-Sung ) - Sungkyunkwan University College of Biotechnology and Bioengineering Department of Integrative Biotechnology

Abstract


Benzo[a]pyrene (B[a]P) is a polycyclic aromatic hydrocarbon and ubiquitous environmental toxin with known harmful effects to human health. Abnormal phenotypes of keratinocytes are closely associated with their exposure to B[a]P. Resorcinol is a component of argan oil with reported anticancer activities, but its mechanism of action and potential effect on B[a]P damage to the skin is unknown. In this study, we investigated the effects of resorcinol on B[a]P-induced abnormal keratinocyte biology and its mechanisms of action in human epidermal keratinocyte cell line HaCaT. Resorcinol suppressed aryl hydrocarbon receptor (AhR) activity as evidenced by the inhibition of B[a]P-induced xenobiotic response element (XRE)-reporter activation and cytochrome P450 1A1 (CYP1A1) expression. In addition, resorcinol attenuated B[a]P-induced nuclear translocation of AhR, and production of ROS and pro-inflammatory cytokines. We also found that resorcinol increased nuclear factor (erythroid-derived 2)-like 2 (Nrf2) activity. Antioxidant response element (ARE)-reporter activity and expression of ARE-dependent genes NAD(P)H dehydrogenase [quinone] 1 (NQO1), heme oxygenase-1 (HO-1) were increased by resorcinol. Consistently, resorcinol treatment induced nuclear localization of Nrf2 as seen by Western analysis. Knockdown of Nrf2 attenuated the resorcinol effects on ARE signaling, but knockdown of AhR did not affect resorcinol activation of Nrf2. This suggests that activation of antioxidant activity by resorcinol is not mediated by AhR. These results indicate that resorcinol is protective against effects of B[a]P exposure. The mechanism of action of resorcinol is inhibition of AhR and activation of Nrf2-mediated antioxidant signaling. Our findings suggest that resorcinol may have potential as a protective agent against B[a]P-containing pollutants.

키워드

Resorcinol; AhR; ARE; HO-1; Nrf2; XRE

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