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Nephrotoxicity Profile of Cadmium Revealed by Proteomics in Mouse Kidney

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Abstract

Cadmium (Cd) is a highly toxic metal and kidney is its main target. However, the molecular effects and associated potential impacts of Cd-accumulated kidney have not been well investigated. In this study, mouse was used as a model to investigate the Cd-induced proteomic profile change in kidney, and a total of 34 differentially expressed proteins were detected by two-dimensional gel electrophoresis (2-DE) and further identified by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). Through Gene Ontology analysis and KEGG pathway annotation, it showed that Cd-regulated kidney metabolism and promoted renal damage and cell migration. By validation of Western blotting and RT-qPCR, metastasis-related proteins LIM and SH3 domain protein 1 (LASP1) and phosphoenolpyruvate carboxykinase/cytosolic [GTP] (PEPCK1) were confirmed to be upregulated; Acyl-CoA synthetase medium-chain family member 3 (ACSM3) was downregulated. Furthermore, carcinoma development-related proteins initiation factor 4A (eIF4A) and pyridoxine-5′-phosphate oxidase (PNPO) were upregulated, and pyridoxal kinase (PK) was downregulated. The downregulation of Na(+)/H(+) exchange regulatory cofactor (NHERF3) might promote renal damage which associated with decrease of transferrin (TRF) in kidney. Taken together, our results revealed proteomic profile of Cd-induced nephrotoxicity and provided data for further insights into the mechanisms of Cd toxicity.

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Abbreviations

Cd:

Cadmium

2-DE:

Two-dimensional electrophoresis

MS:

Mass spectrometry

ACSM3:

Acyl-CoA synthetase medium-chain family member 3

TRF:

Transferrin

PEPCK1:

Phosphoenolpyruvate carboxykinase 1, cytosolic

PNPO:

Pyridoxine 5′-phosphate oxidase

eIF4A:

Eukaryotic translation initiation factor 4A

PDZK1:

PDZ domain containing 1

LASP1:

LIM and SH3 protein 1

PK:

Pyridoxal kinase

MMP-2:

Matrix metalloproteinase 2

MMP-9:

Matrix metalloproteinase 9

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Acknowledgments

We thank the animal house staff for their care of the animals, and Ms. Ye Pan for technical assistance with the 2D gel analysis.

Funding

This work was supported by the National Natural Science Foundation of China (31600952 and 31271272) and the Start-Up Research Funding of Jiangsu University for Distinguished Scholars (5501330001).

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  1. Xi Sun and Yanwei Wang contributed equally to this work.

Authors and Affiliations

  1. Institute of Life Sciences, Jiangsu University, Zhenjiang, 212013, Jiangsu, China

    Xi Sun, Yanwei Wang, Tingya Jiang, Xiao Yuan, Zhen Ren, Alex Tuffour, Yang Zhou, Jie Gu & Haifeng Shi

  2. School of Food and Biological Engineering, Jiangsu University, Zhenjiang, 212013, Jiangsu, China

    Haitao Liu & Haifeng Shi

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  1. Xi Sun
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Contributions

XS, YW, TJ, and XY performed the research; JG and HS designed the research study and contributed essential reagents or tools; XS, YW, TJ, XY, ZR, HL, YZ, JG, and HS analyzed and interpreted the data; XS, YW, TJ, XY, AT, JG, and HS wrote the manuscript. All authors reviewed the manuscript.

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Correspondence to Haifeng Shi.

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Sun, X., Wang, Y., Jiang, T. et al. Nephrotoxicity Profile of Cadmium Revealed by Proteomics in Mouse Kidney. Biol Trace Elem Res 199, 1929–1940 (2021). https://doi.org/10.1007/s12011-020-02312-7

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