Differential profiles of copper-induced ROS generation in human neuroblastoma and astrocytoma cells

Yongchang Qian, Ying Zheng, Liz Abraham, Kenneth S. Ramos, Evelyn Tiffany-Castiglioni

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

To determine neuronal and glial responses to copper (Cu) elevation in the CNS, human neuroblastoma and astrocytoma cells were used to compare their responses to Cu in terms of reactive oxygen species (ROS) generation and expression of enzymes responsible for anti-oxidation. Astrocytoma cells, not neuroblastoma cells, were responsive to Cu and Cu elevation was associated with ROS generation. Intracellular Cu levels as determined by inductively coupled plasma-mass spectrometry (ICP-MS), and expression levels of copper-transporting ATPase (ATP7A) and human copper transporter 1 (hCtr1) as detected by quantitative reverse transcription-polymerase chain reaction (RT-PCR), were comparable in both cell lines. Differences in Cu-induced ROS between two cell lines paralleled superoxide dismutase (SOD)-catalase expression as detected by Western blot analysis. Copper,zinc-SOD (Cu,Zn-SOD) and catalase protein levels were upregulated by Cu in neuroblastoma cells while Cu,Zn-SOD was down-regulated by Cu and catalase level was not changed in astrocytoma cells. Manganese-SOD (Mn-SOD) was not responsive to Cu in either cell line. Furthermore, 78-kDa glucose-regulated protein aggregation and upregulation were observed in Cu-treated astrocytoma cells, but not neuroblastoma cells. These data suggest that neurons use the SOD-catalase system to scavenge Cu-induced ROS while glia rely on the endoplasmic reticulum stress response to compensate for the reduction of ROS scavenging capacity.

Original languageEnglish (US)
Pages (from-to)323-332
Number of pages10
JournalMolecular Brain Research
Volume134
Issue number2
DOIs
StatePublished - Apr 4 2005
Externally publishedYes

Keywords

  • 78-kDa glucose-regulated protein
  • Copper
  • Glia
  • Neurons
  • Reactive oxygen species
  • Superoxide dismutase

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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