Selenium binding protein 1 protects renal tubular epithelial cells from ferroptosis by upregulating glutathione peroxidase 4.

Autor: Zhao W; Department of Nephrology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China., Nikolic-Paterson DJ; Department of Nephrology and Monash University of Medicine, Monash Medical Centre, Clayton, Victoria, Australia., Li K; Department of Nephrology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China., Li Y; Department of Nephrology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China., Wang Y; Department of Nephrology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China., Chen X; Department of Nephrology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China., Duan Z; Department of Nephrology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China., Zhang Y; Department of Nephrology, Xijing Hospital, Xi'an, Shaanxi, China., Liu P; National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China., Lu S; Institute of Molecular and Translational Medicine (IMTM), Department of Biochemistry and Molecular Biology, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China., Fu R; Department of Nephrology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China. Electronic address: furongguo@xjtu.edu.cn., Tian L; Department of Nephrology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China. Electronic address: tianlifang@xjtu.edu.cn.
Jazyk: angličtina
Zdroj: Chemico-biological interactions [Chem Biol Interact] 2024 Apr 25; Vol. 393, pp. 110944. Date of Electronic Publication: 2024 Mar 20.
DOI: 10.1016/j.cbi.2024.110944
Abstrakt: Ferroptosis is a form of programmed cell death involved in various types of acute kidney injury (AKI). It is characterized by inactivation of the selenoprotein, glutathione peroxidase 4 (GPX4), and upregulation of acyl-CoA synthetase long-chain family member 4 (ACSL4). Since urinary selenium binding protein 1 (SBP1/SELENBP1) is a potential biomarker for AKI, this study investigated whether SBP1 plays a role in AKI. First, we showed that SBP1 is expressed in proximal tubular cells in normal human kidney, but is significant downregulated in cases of AKI in association with reduced GPX4 expression and increased ACSL4 expression. In mouse renal ischemia-reperfusion injury (I/R), the rapid downregulation of SBP1 protein levels preceded downregulation of GPX4 and the onset of necrosis. In vitro, hypoxia/reoxygenation (H/R) stimulation in human proximal tubular epithelial (HK-2) cells induced ferroptotic cell death in associated with an acute reduction in SBP1 and GPX4 expression, and increased oxidative stress. Knockdown of SBP1 reduced GPX4 expression and increased the susceptibility of HK-2 cells to H/R-induced cell death, whereas overexpression of SBP1 reduced oxidative stress, maintained GPX4 expression, reduced mitochondrial damage, and reduced H/R-induced cell death. Finally, selenium deficiency reduced GPX4 expression and promoted H/R-induced cell death, whereas addition of selenium was protective against H/R-induced oxidative stress. In conclusion, SBP1 plays a functional role in hypoxia-induced tubular cell death. Enhancing SBP1 expression is a potential therapeutic approach for the treatment of AKI.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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