Involvement of the molecular chaperone Hspa5 in copper homeostasis in astrocytes.

Brain Research
Yongchang QianEvelyn Tiffany-Castiglioni

Abstract

Copper (Cu) ion availability in tissues and cells must be closely regulated within safe limits by Cu transporters and chaperones. Astrocytes play key roles in metal homeostasis and distribution in the brain that are only partially understood. The purpose of this study was to define the role that the protein chaperone Hspa5, also known as Grp78, plays in Cu homeostasis in astrocytes. First passage cultures of primary astrocytes from neonatal rats and cultures of the C6 rat glioma cells were used as models. We found that the level of Cu accumulation in astrocyte cultures increased with Cu concentrations in the medium, and Cu treatment significantly reduced cellular levels of iron (Fe), manganese (Mn) and zinc (Zn). Cu accumulation specifically induced protein expression of Hspa5 but not metallothioneins (MTs) in astrocytes. In C6 cells, Hspa5 was identified as one component of a Cu-binding complex and shown to directly bind Cu. However, the level of Hspa5 expression was not proportional to Cu accumulation in astrocytes and C6 cells: astrocytes expressed low protein levels of Hspa5 compared to C6 cells but accumulated significantly more Cu than did C6 cells. Consistent with this finding, astrocytes expressed a lower level of the C...Continue Reading

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Citations

Nov 20, 2012·Neurochemical Research·Yongchang QianEvelyn Tiffany-Castiglioni
Aug 14, 2015·Neurochemical Research·Felix Bulcke, Ralf Dringen
Aug 26, 2015·Journal of Trace Elements in Medicine and Biology : Organ of the Society for Minerals and Trace Elements (GMS)·Felix BulckeRalf Dringen
Jun 15, 2013·Neurotoxicology·Young Ah SeoMarianne Wessling-Resnick
Sep 18, 2012·Neurochemistry International·Ivo F Scheiber, Ralf Dringen
Mar 1, 2012·Neurotoxicology·Evelyn Tiffany-Castiglioni, Yongchang Qian
Aug 12, 2014·Neurochemical Research·Julie A Moreno, Evelyn Tiffany-Castiglioni
Nov 4, 2016·Neurochemical Research·Arundhati JoshiRalf Dringen
Jun 20, 2012·Biochemistry·Gözde Eskici, Paul H Axelsen
Jan 3, 2013·Journal of Applied Toxicology : JAT·Adriana Alarcón-AguilarMina Königsberg
Jan 30, 2015·Environmental and Molecular Mutagenesis·Lucia MiglioreFabio Coppedè
Dec 10, 2020·Metallomics : Integrated Biometal Science·Ashima BhattacharjeeKaustav Chakraborty

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