Homo-oxidized HSPB1 protects H9c2 cells against oxidative stress via activation of KEAP1/NRF2 signaling pathway

Nian Wang; Xiehong Liu; Ke Liu; Kangkai Wang; Huali Zhang

iScience (Aug 2023)

Homo-oxidized HSPB1 protects H9c2 cells against oxidative stress via activation of KEAP1/NRF2 signaling pathway

Nian Wang,
Xiehong Liu,
Ke Liu,
Kangkai Wang,
Huali Zhang

Affiliations

Nian Wang: Department of Pathophysiology, School of Basic Medicine Science, Central South University, Changsha, China; Sepsis Translational Medicine Key Laboratory of Hunan Province, Central South University, Changsha, Hunan 410078, P.R. China; National Medicine Functional Experimental Teaching Center, Central South University, Changsha, Hunan 410078, P.R. China
Xiehong Liu: Department of Pathophysiology, School of Basic Medicine Science, Central South University, Changsha, China; Sepsis Translational Medicine Key Laboratory of Hunan Province, Central South University, Changsha, Hunan 410078, P.R. China; National Medicine Functional Experimental Teaching Center, Central South University, Changsha, Hunan 410078, P.R. China
Ke Liu: Department of Pathophysiology, School of Basic Medicine Science, Central South University, Changsha, China; Sepsis Translational Medicine Key Laboratory of Hunan Province, Central South University, Changsha, Hunan 410078, P.R. China; National Medicine Functional Experimental Teaching Center, Central South University, Changsha, Hunan 410078, P.R. China
Kangkai Wang: Department of Pathophysiology, School of Basic Medicine Science, Central South University, Changsha, China; Sepsis Translational Medicine Key Laboratory of Hunan Province, Central South University, Changsha, Hunan 410078, P.R. China; National Medicine Functional Experimental Teaching Center, Central South University, Changsha, Hunan 410078, P.R. China; Corresponding author
Huali Zhang: Department of Pathophysiology, School of Basic Medicine Science, Central South University, Changsha, China; Sepsis Translational Medicine Key Laboratory of Hunan Province, Central South University, Changsha, Hunan 410078, P.R. China; National Medicine Functional Experimental Teaching Center, Central South University, Changsha, Hunan 410078, P.R. China; Corresponding author

Journal volume & issue: Vol. 26, no. 8
p. 107443

Abstract

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Summary: Several heat shock proteins are implicated in the endogenous cardioprotective mechanisms, but little is known about the role of heat shock protein beta-1 (HSPB1). This study aims to investigate the oxidation state and role of HSPB1 in cardiomyocytes undergoing oxidative stress and underlying mechanisms. Here, we demonstrate that hydrogen peroxide (H2O2) promotes the homo-oxidation of HSPB1. Cys137 residue of HSPB1 is not only required for it to protect cardiomyocytes against oxidative injury but also modulates its oxidation, phosphorylation at Ser15, and distribution to insoluble cell components after H2O2 treatment. Moreover, Cys137 residue is indispensable for HSPB1 to interact with KEAP1, thus regulating its oxidation and intracellular distribution, subsequently promoting the nuclear translocation of NRF2, and increasing the transcription of GLCM, HMOX1, and TXNRD1. Altogether, these findings provide evidence that Cys137 residue is indispensable for HSPB1 to maintain its redox state and antioxidant activity via activating KEAP1/NRF2 signaling cascade in cardiomyocytes.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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