The hypertension drug, verapamil, activates Nrf2 by promoting p62-dependent autophagic Keap1 degradation and prevents acetaminophen-induced cytotoxicity

Nuclear factor erythroid 2-related factor 2 (Nrf2) provides a cellular defense against oxidative stress by inducing the expression of antioxidant and detoxification enzymes. The calcium antagonist, verapamil, is an FDA-approved drug prescribed for the treatment of hypertension. Here, we show that ve...

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Bibliographic Details
Published inBMB reports Vol. 50; no. 2; pp. 91 - 96
Main Authors Lee, Da Hyun, Park, Jeong Su, Lee, Yu Seol, Sung, Su Haeng, Lee, Yong-ho, Bae, Soo Han
Format Journal Article
LanguageKorean
Published 생화학분자생물학회 28.02.2017
Subjects
APAP
Keap1
Nrf2
Oxidative stress
Verapamil
APAP
Keap1
Oxidative stress
Verapamil
Nrf2
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Summary:Nuclear factor erythroid 2-related factor 2 (Nrf2) provides a cellular defense against oxidative stress by inducing the expression of antioxidant and detoxification enzymes. The calcium antagonist, verapamil, is an FDA-approved drug prescribed for the treatment of hypertension. Here, we show that verapamil acts as a potent Nrf2 activator without causing cytotoxicity, through degradation of Kelch-like ECH-associated protein 1 (Keap1), a Nrf2 repressor. Furthermore, verapamilinduced Keap1 degradation is prominently mediated by a p62-dependent autophagic pathway. Correspondingly, verapamil protects cells from acetaminophen-induced oxidative damage through Nrf2 activation. These results demonstrated the underlying mechanisms for the protective role of verapamil against acetaminophen-induced cytotoxicity. [BMB Reports 2017; 50(2): 91-96]
Bibliography:Korean Society for Biochemistry and Molecular Biology
KISTI1.1003/JNL.JAKO201713056891643
ISSN:1976-6696
1976-670X