Marine Compound 3-Bromo-4,5-dihydroxybenzaldehyde Protects Skin Cells against Oxidative Damage via the Nrf2/HO-1 Pathway

• Main Authors: Yea Seong Ryu, Pincha Devage Sameera Madushan Fernando, Kyoung Ah Kang, Mei Jing Piao, Ao Xuan Zhen, Hee Kyoung Kang, Young Sang Koh, Jin Won Hyun
• Format: Article
• Language: English
• Published: MDPI AG 2019-04-01
• Series: Marine Drugs
• Subjects: keratinocytes; 3-bromo-4,5-dihydroxybenzaldehyde; heme oxygenase-1; nuclear factor erythroid 2-related factor 2; cytoprotection
• Online Access: https://www.mdpi.com/1660-3397/17/4/234

In this study, we aimed to illustrate the potential bio-effects of 3-bromo-4,5-dihydroxybenzaldehyde (3-BDB) on the antioxidant/cytoprotective enzyme heme oxygenase-1 (HO-1) in keratinocytes. The antioxidant effects of 3-BDB were examined via reverse transcription PCR, Western blotting, HO-1 activity assay, and immunocytochemistry. Chromatin immunoprecipitation analysis was performed to test for nuclear factor erythroid 2-related factor 2 (Nrf2) binding to the antioxidant response element of the HO-1 promoter. Furthermore, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that the cytoprotective effects of 3-BDB were mediated by the activation of extracellular signal-regulated kinase (ERK) and protein kinase B (PKB, Akt) signaling. Moreover, 3-BDB induced the phosphorylation of ERK and Akt, while inhibitors of ERK and Akt abrogated the 3-BDB-enhanced levels of HO-1 and Nrf2. Finally, 3-BDB protected cells from H₂O₂- and UVB-induced oxidative damage. This 3-BDB-mediated cytoprotection was suppressed by inhibitors of HO-1, ERK, and Akt. The present results indicate that 3-BDB activated Nrf2 signaling cascades in keratinocytes, which was mediated by ERK and Akt, upregulated HO-1, and induced cytoprotective effects against oxidative stress.