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Kidney Week

Abstract: TH-PO087

Selenoprotein-T Exerts a Protective Role in Cisplatin-Induced AKI by Suppression of ER Stress

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Su, Hua, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HUBEI, China
  • Zhang, Chun, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HUBEI, China
Background

Selenium (Se) is an essential trace element with important roles in human health. Acute kidney injury (AKI) as well as chronic kidney disease are often associated with low serum and tissue levels of Se. Se is incorporated with a wide range of Se-dependent enzymes, also known as selenoproteins, at its active site. Selenoprotein-T (Sel-T), a member of the selenoprotein family, is a novel thioredoxin-like enzyme. However, it's role, especially in ER stress, during renal disease remains unexplored. In this study, we aim to explore the role of Sel-T in the pathogenesis of cisplatin-induced AKI.

Methods

Twenty C57 mice were randomly divided into four groups (n=8-10): sham, AKI-1d, AKI-2d and AKI-4d. Western blot or immunohistochemistry was used to detect the expression of Sel-T, NGAL, cleaved-caspase-3, caspase-12, Bax, Bcl-2 and GRP78. In vitro, NRK-52E cells were exposed to cisplatin (20uM) for 6h, 12h and 24h respectively. Lentivirus transfection or non-specific Sel-T agonists, PACAP and db-cAMP, were utilized to regulate Sel-T before cisplatin stimuli. Flow cytometry and commercial kit were adopted individually for apoptosis and ROS detection.

Results

Comparing to sham groups, the expression of Sel-T was significantly down-regulated in the AKI-4d group. Meanwhile, the levels of NGAL, cleaved-caspase-3 and Bax were increased with the reduction of Bcl-2. Consistently, in vitro Sel-T was lessened, especially after 24h of cisplatin exposure. And Sel-T deficiency aggravated cisplatin induced ER-stress as well as cell apoptosis and ROS generation in NRK-52E cells. Pretreatment of non-specific Sel-T agonists ameliorated the ER stress in cisplatin group.

Conclusion

Sel-T deficiency is occurred in cisplatin-induced AKI in which ER stress-associated apoptosis and oxidative stress are the underlying mechanisms. Hopefully, Sel-T agonists may be effective remedies for cisplatin-induced AKI.

Funding

  • Government Support - Non-U.S.