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

Kyoung Ah Kang,Hee Kyoung Kang,Yea Seong Ryu,Young Sang Koh,Mei Jing Piao,Ao Xuan Zhen,Pincha Devage Sameera Madushan Fernando,Jin Won Hyun

doi:10.3390/md17040234

Kyoung Ah Kang, Hee Kyoung Kang + Show 6 more

Open Access

https://doi.org/10.3390/md17040234

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Journal: Marine Drugs	Publication Date: Apr 19, 2019
Citations: 17	License type: CC BY 4.0

Affiliation: Jeju National University

Abstract

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.

Highlights

The balance between reactive oxygen species (ROS) production and eradication of their toxicity is crucial to maintaining the skin redox balance
heme oxygenase-1 (HO-1) mRNA and protein expression levels were enhanced upon treatment with 10 μM 3-BDB and they were further increased with treatment up to 30 μM 3-BDB compared with the levels in the untreated control cells (Figure 1a)
U0126 and LY294002 notably attenuated HO-1 expression and nuclear factor erythroid 2-related factor 2 (Nrf2) phosphorylation upon 3-BDB treatment (Figure 4b,c). These results suggest that the protective effect of 3-BDB is mediated by extracellular signal-regulated kinase (ERK) and Akt signaling, an important upstream signaling pathway that regulates Nrf2/HO-1

Summary

Introduction

The balance between reactive oxygen species (ROS) production and eradication of their toxicity is crucial to maintaining the skin redox balance. The skin is one of the most important targets of oxidative stress due to ROS from exposure to environmental stimuli and endogenous reactions [1,2]. ROS are a group of free radicals which affect macromolecules (DNA, lipids, and proteins), resulting in the generation of other reactive species [3,4]. ROS are generated during normal metabolism and rapidly induce antioxidant enzymes to maintain cellular homeostasis. The skin possesses an antioxidant defense system; it can be disrupted by excessive ROS, leading to oxidative damage, atopic dermatitis, premature skin aging, and skin cancer [5]. As a cytoprotective signaling mechanism, the Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2)

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