The involvement of copper transporter in lead-induced oxidative stress in astroglia

Yongchang Qian, Ying Zheng, Kenneth Ramos, Evelyn Tiffany-Castiglioni

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28 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)429-438
Number of pages10
JournalNeurochemical Research
Volume30
Issue number4
DOIs
Publication statusPublished - Apr 2005
Externally publishedYes

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Keywords

  • Astroglia
  • Atp7a
  • Copper
  • GRP78
  • Lead
  • ROS

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry

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