Abstract
Aim:
To identify the key proteins involved in the nephrotoxicity induced by andrographolide sodium bisulfite (ASB).
Methods:
Male ICR mice were intravenously administrated with ASB (1000 or 150 mg·kg−1·d−1) for 7 d. The level of malondialdehyde (MDA) and the specific activity of superoxide dismutase (SOD) in kidneys were measured. The renal homogenates were separated by two-dimensional electrophoresis, and the differential protein spots were identified using a matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF)/TOF mass spectrometry.
Results:
The high dose (1000 mg/kg) of ASB significantly increased the MDA content, but decreased the SOD activity as compared to the control mice. The proteomic analysis revealed that 6 proteins were differentially expressed in the high-dose group. Two stress-responsive proteins, ie heat shock cognate 71 kDa protein (HSC70) and peroxiredoxin-6 (PRDX6), were regulated at the expression level. The remaining 4 proteins involving in cellular energy metabolism, including isoforms of methylmalonyl-coenzyme A mutase (MUT), nucleoside diphosphate-linked moiety X motif 19 (Nudix motif19), mitochondrial NADH dehydrogenase 1 alpha subcomplex subunit 10 (NDUFA10) and nucleoside diphosphate kinase B (NDK B), were modified at the post-translational levels.
Conclusion:
Our findings suggest that the mitochondrion is the primary target of ASB and that ASB-induced nephrotoxicity results from oxidative stress mediated by superoxide produced by complex I.
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Acknowledgements
This work was supported by the Science Foundation of Zhejiang Provincial Education Administration Y201016256. We thank Dr Yue-zhi TAO and the members of his laboratory at Zhejiang Academy of Agricultural Sciences for their full support. We also thank Dr Jin-mei ZHOU for critically reading the manuscript.
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Lu, H., Zhang, Xy., Zhou, Yq. et al. Proteomic alterations in mouse kidney induced by andrographolide sodium bisulfite. Acta Pharmacol Sin 32, 888–894 (2011). https://doi.org/10.1038/aps.2011.39
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DOI: https://doi.org/10.1038/aps.2011.39
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