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J Phys Chem B. 2014 Dec 26;118(51):14820-6. doi: 10.1021/jp511056t. Epub 2014 Dec 12.

Molecular Mechanism of Lead-Induced Superoxide Dismutase Inactivation in Zebrafish Livers.

Author information

1
School of Environmental Science and Engineering, China-America CRC for Environment & Health, Shandong University , 27# Shanda South Road, Jinan, Shandong Province 250100, P. R. China.
2
Laboratory of Molecular Design and Drug Discovery, School of Basic Science, China Pharmaceutical University , 24 Tongjiaxiang, Nanjing 210009, China.

Abstract

Lead toxicity has been proved to be related with inducing oxidative stress of organisms and causing inactivation of antioxidant enzymes, the mechanism of which remains unknown. This study investigated and compared superoxide dismutase (Cu/Zn SOD) activity inhibited in lead-treated zebrafish livers and explored the mechanism of SOD inactivation by lead at the molecular level using multiple spectroscopic techniques, isothermal titration calorimetric (ITC) measurement, molecular docking study and ICP-AES detection. Results showed lead exposure decreased SOD activities in zebrafish livers due to direct interactions between lead and SOD, resulting in conformational and functional changes of the enzyme. To be specific, Studies at the molecular level indicated that lead bound into the active site channel of SOD, hindered the path of the catalytic substrate (O(2)(-•)), damaged its skeleton conformation and secondary structure, and interacted with the enzymatically related residue (Arg 141) through electrostatic forces (ΔH < 0, ΔS > 0), and caused the release of Cu(2+) and Zn(2+) from the catalytic pocket of SOD. This work shows a correlation between results on organismal and molecular levels, and obtains a possible model hypothesizing mechanisms of lead toxicity using in vitro experiments instead of in vivo ones.

PMID:
25494975
DOI:
10.1021/jp511056t
[Indexed for MEDLINE]

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