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Kahweol activates the Nrf2/HO-1 pathway by decreasing Keap1 expression independently of p62 and autophagy pathways

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Author(s)
Hye-Young SeoSo-Hee LeeJi-Ha LeeJae Seok HwangMi Kyung KimByoung Kuk Jang
Keimyung Author(s)
Hwang, Jae SeokKim, Mi KyungJang, Byoung Kuk
Department
Dept. of Internal Medicine (내과학)
Journal Title
PLoS One
Issued Date
2020
Volume
15
Issue
10
Abstract
Kahweol is a diterpene found in coffee beans and unfiltered coffee drinks. Several studies have demonstrated that kahweol induces the nuclear factor erythroid-2 related factor 2/ hemeoxygenase-1 (Nrf2/HO-1) pathway; however, the mechanisms involved are currently unknown. Kelch-like ECH-associated protein 1 (Keap1) is a major regulator of Nrf2 expression and is degraded mostly by autophagy. The p62 protein enhances binding to Keap1 and contributes to the activation of Nrf2. Here, we examined the role of Keap1 regulation in the effect of kahweol on the Nrf2/HO-1 pathway in hepatocytes. In AML12 cells and primary mouse hepatocytes, kahweol increased the levels of Nrf2 and HO-1 protein without increasing expression of the Nrf2 mRNA. In addition, kahweol reduced Keap1 protein levels significantly without decreasing Keap1 mRNA levels. Although regulation of the Keap1-Nrf2-pathway by p62-dependent autophagy is well known, we confirmed here that the reduction of Keap1 protein levels by kahweol does not involve p62-dependent autophagy degradation or ubiquitination. In conclusion, kahweol increases the expression of Nrf2 in hepatocytes by inhibiting translation of the Keap1 mRNA.
Keimyung Author(s)(Kor)
황재석
김미경
장병국
Publisher
School of Medicine (의과대학)
Citation
Hye-Young Seo et al. (2020). Kahweol activates the Nrf2/HO-1 pathway by decreasing Keap1 expression independently of p62 and autophagy pathways. PLoS One, 15(10), e0240478. doi: 10.1371/journal.pone.0240478
Type
Article
ISSN
1932-6203
Source
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0240478
DOI
10.1371/journal.pone.0240478
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/43278
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Internal Medicine (내과학)
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