title: Molecular Mechanism of Lead-Induced Superoxide Dismutase Inactivation in Zebrafish Livers.
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.
authors.affiliation: 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.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Rutao
authors.initials: R
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Chunguang
authors.initials: C
authors.lastname: Liu
authors.affiliation: Laboratory of Molecular Design and Drug Discovery, School of Basic Science, China Pharmaceutical University , 24 Tongjiaxiang, Nanjing 210009, China.
authors.forename: Yadong
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000818:Animals; D002151:Calorimetry; D002942:Circular Dichroism; D005260:Female; D007854:Lead / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D062105:Molecular Docking Simulation; D013056:Spectrophotometry, Ultraviolet; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors*; D015027:Zebrafish
chemical_list: D007854:Lead; D013482:Superoxide Dismutase