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

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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.

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Funding

This study was supported by ANID-FONDECYT 1170033 JSA), ANID-STINT-CONICYT CS2018-7940 (JSA, IN, JI, MV), and Swedish Research Council (grant 2015-04222; BM).

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Authors and Affiliations

  1. Molecular and Clinical Pharmacology ICBM Faculty of Medicine, University of Chile, Santiago, Chile

    Raúl Valdes, Alicia Armijo & Juan Segura-Aguilar

  2. Nucleo de Química Y Bioquímica, Facultad de Estudios Interdisciplinarios, Universidad Mayor, Santiago, Chile

    Patricia Muñoz

  3. Department of Laboratory Medicine, Division of Clinical Research Center, Karolinska Institutet, Huddinge, Sweden

    Kjell Hultenby & Andres Hagg

  4. Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden

    Jose Inzunza, Ivan Nalvarte & Mukesh Varshney

  5. Department of Biochemistry and Biophysics, Arrhenius Laboratories, Stockholm University, Stockholm, Sweden

    Bengt Mannervik

Authors
  1. Raúl Valdes
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  2. Alicia Armijo
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  3. Patricia Muñoz
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  8. Mukesh Varshney
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  9. Bengt Mannervik
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  10. Juan Segura-Aguilar
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Correspondence to Juan Segura-Aguilar.

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Valdes, R., Armijo, A., Muñoz, P. et al. Cellular Trafficking of Glutathione Transferase M2-2 Between U373MG and SHSY-S7 Cells is Mediated by Exosomes. Neurotox Res 39, 182–190 (2021). https://doi.org/10.1007/s12640-020-00327-5

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