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

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• 作者：Hao Zhang ; Yang Liu ; Rutao Liu ; Chunguang Liu ; Yadong Chen
• 刊名：Journal of Physical Chemistry B
• 出版年：2014
• 出版时间：December 26, 2014
• 年：2014
• 卷：118
• 期：51
• 页码：14820-14826
• 全文大小：360K
• ISSN：1520-5207

文摘

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鈥揂ES 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 (O₂^{鈥撯€?/sup>), damaged its skeleton conformation and secondary structure, and interacted with the enzymatically related residue (Arg 141) through electrostatic forces (螖H < 0, 螖S > 0), and caused the release of Cu2+ and Zn2+ 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.}