Medicarpin Increases Antioxidant Genes by Inducing NRF2 Transcriptional Level in HeLa Cells.

Jung-Hwan Kim,Jin-Won Hyun,Young-Jin Cho,Mi-Jeong Ahn,Dong-Min Kang

doi:10.3390/antiox11020421

Jung-Hwan Kim, Jin-Won Hyun + Show 3 more

Open Access

https://doi.org/10.3390/antiox11020421

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Abstract

The nuclear factor erythroid-derived 2-related factor 2 (NRF2) plays a pivotal role in the regulation of genes involved in oxidative stress and drug detoxification. Therefore, it is important to find NRF2 inducers to protect cells from excessive oxidative damage. Here, we investigated the effect of medicarpin isolated from the root of Robinia pseudoacacia L. on the activity of NRF2 in HeLa cells. Medicarpin significantly induced the antioxidant response elements (ARE)-luciferase activity in a concentration-dependent manner. Furthermore, medicarpin not only induced HO-1, GCLC, and NQO1 mRNA by translocating NRF2 to the nucleus but also induced the mRNA level of NRF2. To verify the NRF2 induction mechanism by medicarpin, ~2 kb of NRF2 promoter-luciferase assay was executed. As a result, medicarpin significantly induced NRF2-luciferase activity. Moreover, medicarpin strongly inhibited the ubiquitin-dependent proteasomal degradation of NRF2. Thus, medicarpin might protect cells by promoting the NRF2 transcriptional activity.

Highlights

Nuclear factor erythroid 2-related factor 2 (NRF2) is a key transcription factor for the expression of genes responsible for anti-oxidative stress and drug detoxification
HO-1 has been used as a hallmark as an NRF2 target gene and a major antioxidant enzyme for protecting cells from oxidative stress and inflammation
antioxidant response elements (ARE) luciferase assay was performed in HeLa result, medicarpin increased the performed in HeLa cells

Summary

Introduction

Nuclear factor erythroid 2-related factor 2 (NRF2) is a key transcription factor for the expression of genes responsible for anti-oxidative stress and drug detoxification. The role of NRF2 has been implicated in many stress-induced pathophysiological conditions, such as age-related diseases, inflammation, neurodegenerative, metabolic disorders, and various cancers [1,2,3,4]. HO-1 has been used as a hallmark as an NRF2 target gene and a major antioxidant enzyme for protecting cells from oxidative stress and inflammation. The expression of these genes can be controlled by NRF2 through interactions with antioxidant response elements (AREs) located in promoters [13,14]

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