Selenoprotein T protects against cisplatin‐induced acute kidney injury through suppression of oxidative stress and apoptosis

Huang, Jing; Bao, Dian; Lei, Chun‐Tao; Tang, Hui; Zhang, Chun‐Yun; Su, Hua; Zhang, Chun

doi:10.1096/fj.202000180rr

Cited by 26 publications

(16 citation statements)

References 40 publications

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“…As an essential ER protein, SELENOT is required for adaptation in stressful conditions like unfolded protein response [58,59]. It was shown to have protective effects in an ischemia-reperfusion model [84] and may suppress oxidative stress and apoptosis [85]. Since ER stress and proteotoxicity are involved in the molecular pathology of cardiac dysfunction [86], reducing it may be favorable.…”

Section: Protein Folding and Er Stressmentioning

confidence: 99%

Selenium, Selenoproteins, and Heart Failure: Current Knowledge and Future Perspective

Al‐Mubarak

Meer

Bömer

2021

Curr Heart Fail Rep

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Purpose of Review (Mal-)nutrition of micronutrients, like selenium, has great impact on the human heart and improper micronutrient intake was observed in 30–50% of patients with heart failure. Low selenium levels have been reported in Europe and Asia and thought to be causal for Keshan disease. Selenium is an essential micronutrient that is needed for enzymatic activity of the 25 so-called selenoproteins, which have a broad range of activities. In this review, we aim to summarize the current evidence about selenium in heart failure and to provide insights about the potential mechanisms that can be modulated by selenoproteins. Recent Findings Suboptimal selenium levels (<100 μg/L) are prevalent in more than 70% of patients with heart failure and were associated with lower exercise capacity, lower quality of life, and worse prognosis. Small clinical trials assessing selenium supplementation in patients with HF showed improvement of clinical symptoms (NYHA class), left ventricular ejection fraction, and lipid profile, while governmental interventional programs in endemic areas have significantly decreased the incidence of Keshan disease. In addition, several selenoproteins are found impaired in suboptimal selenium conditions, potentially aggravating underlying mechanisms like oxidative stress, inflammation, and thyroid hormone insufficiency. Summary While the current evidence is not sufficient to advocate selenium supplementation in patients with heart failure, there is a clear need for high level evidence to show whether treatment with selenium has a place in the contemporary treatment of patients with HF to improve meaningful clinical endpoints. Graphical abstract

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Section: Protein Folding and Er Stressmentioning

confidence: 99%

Selenium, Selenoproteins, and Heart Failure: Current Knowledge and Future Perspective

Al‐Mubarak

Meer

Bömer

2021

Curr Heart Fail Rep

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“…Moreover, this regimen resulted in stress injuries [ 33 ]. In addition, SELENOT protects kidney cells against cisplatin-induced apoptosis [ 34 ]. These observations go along with the notion that ER-resident selenoproteins are critical in cellular stress responses [ 35 ].…”

Section: Resultsmentioning

confidence: 99%

Selenoprotein T Protects Endothelial Cells against Lipopolysaccharide-Induced Activation and Apoptosis

et al. 2021

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Sepsis is an exaggerated immune response upon infection with lipopolysaccharide (LPS) as the main causative agent. LPS-induced activation and apoptosis of endothelial cells (EC) can lead to organ dysfunction and finally organ failure. We previously demonstrated that the first twenty amino acids of the Apurinic/Apyrimidinic Endodeoxyribonuclease 1 (APEX1) are sufficient to inhibit EC apoptosis. To identify genes whose regulation by LPS is affected by this N-terminal APEX1 peptide, EC were transduced with an expression vector for the APEX1 peptide or an empty control vector and treated with LPS. Following RNA deep sequencing, genes upregulated in LPS-treated EC expressing the APEX1 peptide were identified bioinformatically. Selected candidates were validated by semi-quantitative real time PCR, a promising one was Selenoprotein T (SELENOT). For functional analyses, an expression vector for SELENOT was generated. To study the effect of SELENOT expression on LPS-induced EC activation and apoptosis, the SELENOT vector was transfected in EC. Immunostaining showed that SELENOT was expressed and localized in the ER. EC transfected with the SELENOT plasmid showed no activation and reduced apoptosis induced by LPS. SELENOT as well as APEX1(1-20) can protect EC against activation and apoptosis and could provide new therapeutic approaches in the treatment of sepsis.

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“…It has been reported that SELENOT could protect dopaminergic neurons in mouse models of Parkinson's disease because of its crucial oxidoreductase activity [9]. In a recent study, Selenot knockdown aggravated cisplatin-induced apoptosis in NRK-52E cells, a kind of rat renal tubular epithelial cells, indicating that SELENOT prevented mice from cisplatin-induced acute kidney injury (AKI) by suppressing oxidative stress and cell apoptosis [20]. However, the function of SELENOT remains little known.…”

Section: Discussionmentioning

confidence: 99%

Hepatic Proteomic Analysis of Selenoprotein T Knockout Mice by TMT: Implications for the Role of Selenoprotein T in Glucose and Lipid Metabolism

Feng

Liu

et al. 2021

IJMS

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Selenoprotein T (SELENOT, SelT), a thioredoxin-like enzyme, exerts an essential oxidoreductase activity in the endoplasmic reticulum. However, its precise function remains unknown. To gain more understanding of SELENOT function, a conventional global Selenot knockout (KO) mouse model was constructed for the first time using the CRISPR/Cas9 technique. Deletion of SELENOT caused male sterility, reduced size/body weight, lower fed and/or fasting blood glucose levels and lower fasting serum insulin levels, and improved blood lipid profile. Tandem mass tag (TMT) proteomics analysis was conducted to explore the differentially expressed proteins (DEPs) in the liver of male mice, revealing 60 up-regulated and 94 down-regulated DEPs in KO mice. The proteomic results were validated by western blot of three selected DEPs. The elevated expression of Glycogen [starch] synthase, liver (Gys2) is consistent with the hypoglycemic phenotype in KO mice. Furthermore, the bioinformatics analysis showed that Selenot-KO-induced DEPs were mainly related to lipid metabolism, cancer, peroxisome proliferator-activated receptor (PPAR) signaling pathway, complement and coagulation cascades, and protein digestion and absorption. Overall, these findings provide a holistic perspective into SELENOT function and novel insights into the role of SELENOT in glucose and lipid metabolism, and thus, enhance our understanding of SELENOT function.

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Selenoprotein T protects against cisplatin‐induced acute kidney injury through suppression of oxidative stress and apoptosis

Cited by 26 publications

References 40 publications

Selenium, Selenoproteins, and Heart Failure: Current Knowledge and Future Perspective

Selenium, Selenoproteins, and Heart Failure: Current Knowledge and Future Perspective

Selenoprotein T Protects Endothelial Cells against Lipopolysaccharide-Induced Activation and Apoptosis

Hepatic Proteomic Analysis of Selenoprotein T Knockout Mice by TMT: Implications for the Role of Selenoprotein T in Glucose and Lipid Metabolism

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