Wang Nian, Liu Xiehong, Liu Ke, Wang Kangkai, Zhang Huali
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.
iScience. 2023 Jul 20;26(8):107443. doi: 10.1016/j.isci.2023.107443. eCollection 2023 Aug 18.
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 (HO) 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 HO 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 , , and . 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.
几种热休克蛋白参与内源性心脏保护机制，但关于热休克蛋白β-1（HSPB1）的作用知之甚少。本研究旨在探讨HSPB1在经历氧化应激的心肌细胞中的氧化状态和作用及其潜在机制。在此，我们证明过氧化氢（HO）促进HSPB1的同源氧化。HSPB1的半胱氨酸137残基不仅是其保护心肌细胞免受氧化损伤所必需的，而且还调节其氧化、丝氨酸15位点的磷酸化以及HO处理后向不溶性细胞成分的分布。此外，半胱氨酸137残基对于HSPB1与KEAP1相互作用不可或缺，从而调节其氧化和细胞内分布，随后促进NRF2的核转位，并增加 、 和 的转录。总之，这些发现提供了证据，表明半胱氨酸137残基对于HSPB1通过激活心肌细胞中的KEAP1/NRF2信号级联来维持其氧化还原状态和抗氧化活性是不可或缺的。
