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

• Published in: Brain research. Molecular brain research. Vol. 134; no. 2; pp. 323 - 332
• Main Authors: Qian, Yongchang, Zheng, Ying, Abraham, Liz, Ramos, Kenneth S., Tiffany-Castiglioni, Evelyn
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 04.04.2005; Elsevier
• Subjects: 78-kDa glucose-regulated protein; Adenosine Triphosphatases - genetics; Adenosine Triphosphatases - metabolism; Astrocytoma - pathology; Biological and medical sciences; Blotting, Western - methods; Catalase - metabolism; Cation Transport Proteins - genetics; Cation Transport Proteins - metabolism; Cell Line, Tumor; Copper; Copper - metabolism; Copper Sulfate - pharmacology; Copper-transporting ATPases; Dose-Response Relationship, Drug; Drug Interactions; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - drug effects; Glia; Green Fluorescent Proteins - biosynthesis; Green Fluorescent Proteins - pharmacology; Heat-Shock Proteins - metabolism; Humans; Mass Spectrometry - methods; Medical sciences; Metallochaperones; Molecular Chaperones - genetics; Molecular Chaperones - metabolism; Neuroblastoma - pathology; Neurology; Neurons; Reactive oxygen species; Reactive Oxygen Species - metabolism; Recombinant Fusion Proteins - biosynthesis; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; Reverse Transcriptase Polymerase Chain Reaction - methods; RNA, Messenger - biosynthesis; Superoxide dismutase; Superoxide Dismutase - metabolism; Tumors of the nervous system. Phacomatoses; Vertebrates: nervous system and sense organs; Reactive oxygen species; 78-kDa glucose-regulated protein; Neurons; Superoxide dismutase; Disorders of the Nervous System; Glia; Copper; Human; Nervous system diseases; Enzyme; Neuroglia; Glucose; Cell line; Neuron; Glioma; Central nervous system disease; Tumor; Oxidoreductases; Astrocytoma
• ISSN: 0169-328X; 1872-6941
• DOI: 10.1016/j.molbrainres.2004.11.004

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.