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Nitrative and oxidative modifications of enolase are associated with iron in iron-overload rats and in vitro

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Abstract

Iron overload is one of the most common iron-related toxicities, and liver is the major organ that is injured. Although oxidative stress is well accepted in the pathological mechanism of iron overload, nitrative modification in liver and the role of iron are relatively unknown. In this work, the nitrative and oxidative stress in liver was investigated in an iron-overload rat model. It was found that after 15 weeks of iron dextran administration, consistent with the increase of iron content in rat liver, both protein tyrosine nitration and protein oxidation were clearly elevated. By means of immunoprecipitation analysis, it was found that enolase nitration and oxidation status were significantly increased in iron-overload liver, whereas both α-enolase expression and activity were clearly decreased. The effects of different forms of iron on NaNO2–H2O2- and peroxynitrite (ONOO−)-dependent enolase nitration and oxidation were further investigated in vitro to elucidate the possible role of iron in enolase dysfunction in vivo. Compared with EDTA–Fe(III), ferric citrate, and ferritin, heme (hemin and hemoglobin) showed higher efficiency in catalyzing protein nitration in both models. Besides the major contribution of free iron (Fe2+ and Fe3+) to catalyze protein oxidation, Fe2+ also directly acted as a competitive inhibitor and produced a significant decrease in enzyme activity. These results suggest that the existence of various forms of iron is an important contributing factor to the elevated nitrative/oxidative modifications and diminished activity of α-enolase in the development and progress of iron-overload-associated syndromes.

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (Nos. 30300073 and 30670481), the Program for New Century Excellent Talents in University (No. NCET-05-0649), and the Fundamental Research Funds for the Central Universities (HUST No. 2010ZD010).

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Authors and Affiliations

  1. Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica, Department of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan, 430074, People’s Republic of China

    Naihao Lu, Xueli Li, Jinyang Li, Wenjing Xu, Hailing Li & Zhonghong Gao

  2. Key Laboratory of Small Functional Organic Molecule, Ministry of Education and College of Life Science, Jiangxi Normal University, 99 Ziyang Road, Nanchang, 330022, Jiangxi, People’s Republic of China

    Naihao Lu

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  1. Naihao Lu
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  2. Xueli Li
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  3. Jinyang Li
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  4. Wenjing Xu
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  5. Hailing Li
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  6. Zhonghong Gao
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Correspondence to Zhonghong Gao.

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Lu, N., Li, X., Li, J. et al. Nitrative and oxidative modifications of enolase are associated with iron in iron-overload rats and in vitro. J Biol Inorg Chem 16, 481–490 (2011). https://doi.org/10.1007/s00775-010-0747-6

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  • DOI: https://doi.org/10.1007/s00775-010-0747-6

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