We are analyzing https://link.springer.com/article/10.1007/s11064-005-2677-1.

Title:
The Involvement of Copper Transporter in Lead-induced Oxidative Stress in Astroglia | Neurochemical Research
Description:
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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Topics {✒️}

gov/nceh/lead/guide/guide97 month download article/chapter 78 kda glucose-regulated protein n-acetylcysteine free radic copper-induced ros generation lead-induced endoplasmic reticulum lead-induced oxidative stress pb-induced oxidative stress copper-transporting atpase nat lead-exposed c57bl/6 mice low-level lead exposure human menkes protein p1b-type atpase endoplasmic reticulum dysfunction privacy choices/manage cookies bound transition metals peroxidative stress selectively full article pdf cultured hippocampal astrocytes grp94 protein induction induce oxidative stress cu-transporting atpase grp78 compartmentalized redistribution n-terminal domains oxidative defense system n-acetylcysteine exposure lead targets grp78 inorganic lead toxicol situ oxidative catalysis bone lead levels blood lead concentrations heavy metal-binding metal-binding repeat prospective study neurotoxicol menkes disease proteins european economic area reactive oxygen species related subjects neuroglial enzyme activities ii mcgraw-hill primary neuronal cultures signal transduction pathway veterinary integrative biosciences blood lead concentration rat brain res central nervous system copper oxide nanoparticles bind copper selectively nervous system cancer lead neurotoxicity neurochem

Questions {❓}

Vainio (1997) Lead and cancer—association or causation?

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      description: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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