Inhibition of USP14 Suppresses ROS-dependent Ferroptosis and Alleviates Renal Ischemia/Reperfusion Injury

The ubiquitin-specific protease 14 (USP14) is a deubiquitinating enzyme, its inhibitor was reported could alleviate the ischemia/reperfusion (I/R)-stimulated cerebral neuronal damage. However, its specific role in I/R-induced acute kidney injury (AKI) remains unclear. We established hypoxia/reoxygen...

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Bibliographic Details
Published in:Cell biochemistry and biophysics 2023-03, Vol.81 (1), p.87-96
Main Authors: Pan, Jie, Zhao, Jing, Feng, Ling, Xu, Xiaoli, He, Zhiting, Liang, Wei
Format: Article
Language:English
Subjects:
Acetylcysteine
Acute Kidney Injury - drug therapy
Animals
Biochemistry
Biological and Medical Physics
Biomedical and Life Sciences
Biophysics
Biotechnology
Cell Biology
Cell death
Cell injury
Ferroptosis
Hypoxia
Inflammation
Inhibitors
Injuries
Ischemia
Kidney - metabolism
Kidneys
Life Sciences
Mice
Original Paper
Oxidative stress
Pharmacology/Toxicology
Reactive oxygen species
Reactive Oxygen Species - metabolism
Reperfusion
Reperfusion Injury - drug therapy
Reperfusion Injury - metabolism
siRNA
Ubiquitin
Ubiquitin Thiolesterase
Ubiquitin-specific proteinase
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Summary:The ubiquitin-specific protease 14 (USP14) is a deubiquitinating enzyme, its inhibitor was reported could alleviate the ischemia/reperfusion (I/R)-stimulated cerebral neuronal damage. However, its specific role in I/R-induced acute kidney injury (AKI) remains unclear. We established hypoxia/reoxygenation (H/R)-induced HK-2 cell injury model in vitro and I/R-induced kidney injury mice model in vivo. The expression or activity of USP14 was inhibited by siRNA or IU1, a small molecule inhibitor of USP14. ROS were scavenged by N-acetyl-cysteine (NAC). Biochemical index analysis and hematoxylin & eosin (H&E) staining were performed to evaluate renal injury. The results indicated that USP14 was upregulated in H/R-induced HK-2 cells and kidney tissues of I/R mice. Inhibition of USP14 suppressed the cell death, inflammatory, oxidative stress and reactive oxygen species (ROS)-dependent ferroptosis of H/R-induced HK-2 cells. What’s more, IU1 and NAC effectively alleviated renal injury of I/R mice. In summary, this study suggested that inhibition of USP14 protected renal from I/R injury.
ISSN:1085-9195
1559-0283
DOI:10.1007/s12013-022-01107-y