Function of Metallothionein-3 in Neuronal Cells: Do Metal Ions Alter Expression Levels of MT3?

Jamie Bousleiman; Alexa Pinsky; Sohee Ki; Angela Su; Irina Morozova; Sergey Kalachikov; Amen Wiqas; Rae Silver; Mary Sever; Rachel Narehood Austin

doi:10.3390/ijms18061133

Function of Metallothionein-3 in Neuronal Cells: Do Metal Ions Alter Expression Levels of MT3?

Int J Mol Sci. 2017 May 25;18(6):1133. doi: 10.3390/ijms18061133.

Authors

Jamie Bousleiman¹, Alexa Pinsky², Sohee Ki³, Angela Su⁴, Irina Morozova⁵, Sergey Kalachikov⁶, Amen Wiqas⁷, Rae Silver^{8

9

10}, Mary Sever¹¹, Rachel Narehood Austin¹²

Affiliations

¹ Department of Chemistry, Barnard College of Columbia University, New York, NY 10027, USA. jb3424@barnard.edu.
² Department of Chemistry, Barnard College of Columbia University, New York, NY 10027, USA. amp2248@barnard.edu.
³ Department of Chemistry, Barnard College of Columbia University, New York, NY 10027, USA. ski@barnard.edu.
⁴ Department of Chemistry, Barnard College of Columbia University, New York, NY 10027, USA. su.angela1@gmail.com.
⁵ Center for Genome Technology and Biomolecular Engineering, Department of Chemical Engineering, Columbia University, New York, NY 10027, USA. im198@columbia.edu.
⁶ Center for Genome Technology and Biomolecular Engineering, Department of Chemical Engineering, Columbia University, New York, NY 10027, USA. sk363@columbia.edu.
⁷ Department of Biology, Barnard College of Columbia University, New York, NY 10027, USA. aw2868@barnard.edu.
⁸ Department of Psychology and Program in Neuroscience, Barnard College of Columbia University, New York, NY 10027, USA. rae.silver@columbia.edu.
⁹ Department of Psychology, Columbia University, New York, NY 10027, USA. rae.silver@columbia.edu.
¹⁰ Department of Pathology and Cell Biology Columbia Health Sciences, New York, NY 10027, USA. rae.silver@columbia.edu.
¹¹ Department of Chemistry, Barnard College of Columbia University, New York, NY 10027, USA. msever@barnard.edu.
¹² Department of Chemistry, Barnard College of Columbia University, New York, NY 10027, USA. raustin@barnard.edu.

Abstract

A study of factors proposed to affect metallothionein-3 (MT3) function was carried out to elucidate the opaque role MT3 plays in human metalloneurochemistry. Gene expression of Mt2 and Mt3 was examined in tissues extracted from the dentate gyrus of mouse brains and in human neuronal cell cultures. The whole-genome gene expression analysis identified significant variations in the mRNA levels of genes associated with zinc homeostasis, including Mt2 and Mt3. Mt3 was found to be the most differentially expressed gene in the identified groups, pointing to the existence of a factor, not yet identified, that differentially controls Mt3 expression. To examine the expression of the human metallothioneins in neurons, mRNA levels of MT3 and MT2 were compared in BE(2)C and SH-SY5Y cell cultures treated with lead, zinc, cobalt, and lithium. MT2 was highly upregulated by Zn²⁺ in both cell cultures, while MT3 was not affected, and no other metal had an effect on either MT2 or MT3.

Keywords: MT3; dentate gyrus; gene expression; lead neurotoxicity; metalloneurochemistry; metallothionein; microarrays.

MeSH terms

Animals
Dentate Gyrus / metabolism
Gene Expression Profiling
Gene Expression Regulation / drug effects
Ions / metabolism
Ions / pharmacology
Metallothionein / genetics*
Metallothionein / metabolism*
Metallothionein 3
Metals / metabolism
Metals / pharmacology
Mice
Neurons / drug effects
Neurons / metabolism*
Proteostasis / genetics
Zinc / metabolism

Substances

Ions
Metallothionein 3
Metals
Mt3 protein, mouse
Metallothionein
Zinc