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

Li, Ké; Feng, Tiejun; Liu, Leyan; Li, Hongmei; Huang, Kaixun; Zhou, Jun

doi:10.3390/ijms22168515

Cited by 8 publications

(3 citation statements)

References 64 publications

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“…Being a major protein disulfide reductase in the cell, TXNRD1 is involved in the control of antioxidant defense [ 53 ]. Moreover, SELENOT, also an ER-resident selenoprotein, has been reported to be involved in the regulation of glucose metabolism [ 54 , 55 ]. However, we found that the expression levels of TXNRD1 and SELENOT did not change in the livers of KO mice at all ages ( Figure S2 ), suggesting that SELENOF KO had no significant effect on their expression.…”

Section: Discussionmentioning

confidence: 99%

Selenoprotein F Knockout Caused Glucose Metabolism Disorder in Young Mice by Disrupting Redox Homeostasis

Yun

Zhou

et al. 2022

Antioxidants

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Selenoprotein F (SELENOF) might play an important role in maintaining human health since an increasing number of studies have linked SELENOF deficiency to various pathologies such as cancer and neurodegeneration. We have previously reported on glucose metabolism disorders in SELENOF knockout mice, which imply a novel biological function of SELENOF in glucose metabolism. However, the underlying mechanism and whether the effect of SELENOF on glucose metabolism is age-dependent remain unknown. In the present study, we compare the metabolic phenotype in more detail as well as the oxidative stress parameters in SELENOF knockout mice (C57BL/6J background) and naïve C57BL/6J mice of different ages (12, 16 and 21 weeks old). The results showed that SELENOF knockout caused glucose metabolism disorders only in young mice, especially in 12-week-old mice, characterized by hyperglycemia, serum insulin reduction, impaired glucose tolerance, decreased insulin sensitivity, decreased glucose catabolism, increased gluconeogenesis and impaired insulin signaling pathway. These abnormalities gradually improved with age and disappeared in knockout mice at 21 weeks old. Furthermore, before 16 weeks old, SELENOF knockout mice showed increased lipid peroxidation and decreased glutathione/glutathione disulfide ratio and glutathione peroxidase activity in the serum and liver. Furthermore, the expression of glutathione peroxidase 1 significantly reduced in the liver and pancreas. Our findings suggest that SELENOF knockout might cause glucose metabolism disorders in young mice via the disruption of redox homeostasis.

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Section: Discussionmentioning

confidence: 99%

Selenoprotein F Knockout Caused Glucose Metabolism Disorder in Young Mice by Disrupting Redox Homeostasis

Yun

Zhou

et al. 2022

Antioxidants

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“…This study found that LIRA can reverse the expression of SelT in the model group, which may be related to oxidative stress, etc ( 25 ). TXNIP, which is involved in the activation of the NLRP3 inflammasome, is closely related to the onset of type 2 diabetes mellitus ( 26 ). As claimed by Bai S et al, MMP-2 is related to the progression of chronic diabetes complications, and exosomal circ_DLGAP4 regulates the expression of miR-143 and targets the ERBB3/NF-κB/MMP-2 axis, which triggers the occurrence of diabetic nephropathy ( 27 ).…”

Section: Discussionmentioning

confidence: 99%

Tandem mass tag-based proteomic profiling revealed potential therapeutic targets and mechanisms of liraglutide for the treatment of impaired glucose tolerance

Guo

Han²,

Xu³

et al. 2022

Front. Endocrinol.

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ObjectiveBased on the tandem mass tag (TMT) technique, our study investigated the potential therapeutic targets of Liraglutide (LIRA) on streptozotocin (STZ) induced impaired glucose tolerance (IGT) in rats and discuss the biological mechanism of the drug against IGT.Methods10 rats were randomly selected from 31 male wistar rats of specific pathogen free (SPF) grade as control group and fed with conventional chow, offered the remaining rats a high fat and high sugar (HFSD) diet combined with an intraperitoneal injection of STZ to establish the IGT model, and excluded 2 non-model rats. Specifically, the model rats were randomly divided into Model group (n=10) and LIRA group (n=9). In addition, the LIRA group was subcutaneously injected with 0.06 mg/kg LIRA, during which the metabolic parameters including body weight and fasting blood glucose were recorded. After 8 weeks, samples were taken under anesthesia. Then, the cell morphology was observed using HE staining, and immunofluorescence was performed on the pancreatic tissues of the three groups of rats. Besides, the expression of differential proteins in pancreatic tissues of the three groups of rats was determined by the TMT proteomic labeling. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) biological function analysis were performed on the intersection of Model and LIRA differential proteins.ResultsLIRA could not only significantly reduce blood glucose levels but also improve islet cell morphology and function in IGT rats. Among the differential proteins between the model group and the blank group, 44 were reversed after LIRA treatment, of which 14 were up-regulated, while 30 were down-regulated, including PPIF, MPRIP, CYP51, TXNL1, BCL-2, etc. (FC>1.1 or<0.909, P<0.05). According to the GO and KEGG analysis results, it was related to biological processes such as fatty acid metabolism and adipocyte generation, which involved multiple signaling pathways regulating the function of islet cells, such as MAPK, PI, Ras, FcγR, and unsaturated fatty acids, and pyruvate metabolism.ConclusionTo sum up, LIRA participated in anti-IGT therapy through regulation of multiple target proteins and biological functions. This study is of great reference for further exploring the mechanism of action of LIRA at the protein level of IGT.

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“…19 Then, 100 μg of each peptide mixture sampled was labeled, using tandem mass tag (TMT)-6plex reagent (Thermo Fisher Scientific, 90,064CH, USA), according to the manufacturer's instructions. 20 In brief, 200 μg of digested proteins were mixed with 30 μL standard buffer (4% SDS, 100 mM DTT, 150 mM Tris-HCI, pH 8.0). The detergent, DTT and other low molecular weight components were then removed by repeated ultrafiltration (MicroCon units, 10 kDa) in uric acid buffer (8 M urea, 150 mM Tris-HCl pH 8.0).…”

Section: Proteolysismentioning

confidence: 99%

Analysis of kidney proteomes to identify biological pathways associated with vancomycin-induced nephrotoxicity in mice by tandem mass tag-labeled quantitative and parallel reaction monitoring phosphoproteomics

Yang

Yin

et al. 2023

Hum Exp Toxicol

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Vancomycin (VCM)-induced nephrotoxicity impedes its treatment applications. Thus, it is important to clarify the relevant mechanism. This study investigated phosphoprotein changes attributable to the VCM nephrotoxicity mechanisms. Biochemical, pathological and phosphoproteomic analyses based on C57BL/6 mice were performed to explore the mechanisms.VCM-treated mice showed increased levels of blood urea nitrogen and creatinine, and signs of acute tubular necrotic lesions. Phosphoproteomic profiling identified 3025 differentially phosphorylated phosphopeptides between the model and control group. Gene Ontology enrichment analysis demonstrated that Molecular Function “oxidoreductase activity” and Cellular Component “peroxisome” were markedly enriched. KEGG pathway analysis identified an enrichment in peroxisome pathway and PPAR (peroxisome proliferator-activated receptor) signaling pathways. Parallel reaction monitoring analysis revealed a significant downregulation of CAT, SOD-1, AGPS, DHRS4, and EHHADH at phosphorylation level by VCM. Notably, the phosphorylation of ACO, AMACR, and SCPX was downregulated by VCM, which are the fatty acid β-oxidation-related proteins involved in PPAR signaling pathways. The phosphorylated PEX5 involved in peroxisome biogenesis was upregulated by VCM. Collectively, these findings indicated that VCM-induced nephrotoxicity is closely associated with peroxisome pathway and PPAR signaling pathways. The current study provides important insight into the mechanisms of VCM nephrotoxicity and will aid in the development of preventive and therapeutic strategies against this nephropathy.

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

Cited by 8 publications

References 64 publications

Selenoprotein F Knockout Caused Glucose Metabolism Disorder in Young Mice by Disrupting Redox Homeostasis

Selenoprotein F Knockout Caused Glucose Metabolism Disorder in Young Mice by Disrupting Redox Homeostasis

Tandem mass tag-based proteomic profiling revealed potential therapeutic targets and mechanisms of liraglutide for the treatment of impaired glucose tolerance

Analysis of kidney proteomes to identify biological pathways associated with vancomycin-induced nephrotoxicity in mice by tandem mass tag-labeled quantitative and parallel reaction monitoring phosphoproteomics

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