Cellular Trafficking of Glutathione Transferase M2-2 Between U373MG and SHSY-S7 Cells is Mediated by Exosomes

Neurotox Res. 2021 Apr;39(2):182-190. doi: 10.1007/s12640-020-00327-5. Epub 2021 Feb 8.

Abstract

The enzyme glutathione transferase M2-2, expressed in human astrocytes, increases its expression in the presence of aminochrome and catalyzes the conjugation of aminochrome, preventing its toxic effects. Secretion of the enzyme glutathione transferase M2-2 from U373MG cells, used as a cellular model for astrocytes, has been reported, and the enzyme is taken up by neuroblastoma SYSH-S7 cells and provide protection against aminochrome. The present study provides evidence that glutathione transferase M2-2 is released in exosomes from U373MG cells, thereby providing a means for intercellular transport of the enzyme. With particular relevance to Parkinson disease and other degenerative conditions, we propose a new mechanism by which astrocytes may protect dopaminergic neurons against the endogenous neurotoxin aminochrome.

Keywords: Aminochrome; Astrocytes; Dopamine; Dopaminergic neurons; Exosomes; Neuroprotection; Parkinson´s disease.

MeSH terms

  • Astrocytes / metabolism*
  • Cell Line, Tumor
  • Dopaminergic Neurons / metabolism
  • Exosomes / metabolism*
  • Glutathione Transferase / metabolism*
  • Humans
  • Protein Transport*

Substances

  • Glutathione Transferase
  • glutathione S-transferase Mu 2