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The Involvement of Copper Transporter in Lead-induced Oxidative Stress in Astroglia

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Abstract

Lead (Pb), depositing primarily in astroglia in the brain, is a well-known neurotoxicant and a risk factor for neurologic disorders. Pb has been reported to induce oxidative stress by probably the disturbance of copper (Cu) homeostasis in astroglia. Thus, we hypothesized that Pb-induced oxidative stress is initiated by interfering with Cu transporter in astroglia. In this study, we observed Pb-induced oxidative stress as indicated by reactive oxygen species (ROS) augmentation and GRP78 and GRP94 protein induction, and it was parallel to Cu accumulation intracellularly by Pb. To further address Cu transporter as a potential Pb target, a heavy metal-binding (HMB) domain of Cu-transporting ATPase (Atp7a) was overexpressed and purified. Evidence showed that one molecule of HMB chelated 11 Pb ions or seven Cu ions and that Pb competed with Cu for binding to HMB. These findings suggest that Pb-induced oxidative stress results from the impairment of Cu metabolism by Pb targeting of Atp7a.

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Authors and Affiliations

  1. Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX, 77843–4458, USA

    Yongchang Qian, Ying Zheng & Evelyn Tiffany-Castiglioni

  2. Department of Biochemistry and Molecular Biology and Center for Genetics and Molecular Medicine, University of Louisville Health Sciences Center, Louisville, KY, 40292, USA

    Kenneth S. Ramos

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  1. Yongchang Qian
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  2. Ying Zheng
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  4. Evelyn Tiffany-Castiglioni
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Qian, Y., Zheng, Y., Ramos, K.S. et al. The Involvement of Copper Transporter in Lead-induced Oxidative Stress in Astroglia. Neurochem Res 30, 429–438 (2005). https://doi.org/10.1007/s11064-005-2677-1

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