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The mechanism for heme to prevent Aβ1–40 aggregation and its cytotoxicity

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Abstract

The β-amyloid peptide (Aβ) aggregation in the brain, known as amyloid plaques, is a hallmark of Alzheimer’s disease (AD). The aberrant interaction of Cu2+ ion with Aβ potentiates AD by inducing Aβ aggregation and generating neurotoxic reactive oxygen species (ROS). In this study, the biosynthesized recombinant Aβ1–40 was, for the first time, used to investigate the mechanism for heme to prevent Aβ1–40 aggregation and its cytotoxicity. Cell viability studies of SH-SY5Y cells and rat primary hippocampal neurons showed that exogenous heme can protect the cells by reducing cytotoxicity in the presence of Cu2+ and/or Aβ1–40. UV–vis spectroscopy, circular dichroism spectroscopy, and differential pulse voltammetry were applied to examine the interaction between heme and Aβ1–40. It was proven that a heme–Aβ1–40 complex is formed and can stabilize the α-helix structure of Aβ1–40 to inhibit Aβ1–40 aggregation. The heme–Aβ1–40 complex possesses peroxidase activity and it may catalyze the decomposition of H2O2, reduce the generation of ROS downstream, and ultimately protect the cells. These results indicated that exogenous heme is able to alleviate the cytotoxicity induced by Aβ1–40 and Cu2+. This information may be a foundation to develop a potential strategy to treat AD.

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Acknowledgments

This work was supported in part by the National Natural Science Foundation of China (no. 20771029; no. 29281005), Shanghai Pujiang Talent Project (08pj14017), Shanghai Leading Academic Discipline Project (B108), and the Program for the Platform of New Medicine Creation (no. 2009ZX09301-011).

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Authors and Affiliations

  1. Institutes of Biomedical Sciences, Fudan University, Shanghai, 200433, China

    Qingui Bao, Ying Luo, Wei Li & Xiangshi Tan

  2. Department of Chemistry, Fudan University, Shanghai, 200433, China

    Zhong-Xian Huang & Xiangshi Tan

  3. State Key Laboratory of Medical Neurobiology, Shanghai Medical College of Fudan University, Shanghai, China

    Xiaobo Sun & Cuiqing Zhu

  4. Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX, 77843, USA

    Pingwei Li

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  1. Qingui Bao
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  2. Ying Luo
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  3. Wei Li
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  4. Xiaobo Sun
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  5. Cuiqing Zhu
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  7. Zhong-Xian Huang
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  8. Xiangshi Tan
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Correspondence to Xiangshi Tan.

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Bao, Q., Luo, Y., Li, W. et al. The mechanism for heme to prevent Aβ1–40 aggregation and its cytotoxicity. J Biol Inorg Chem 16, 809–816 (2011). https://doi.org/10.1007/s00775-011-0783-x

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  • DOI: https://doi.org/10.1007/s00775-011-0783-x

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