Glutaredoxin 2 promotes SP-1-dependent CSPG4 transcription and migration of wound healing NG2 glia and glioma cells: Enzymatic Taoism.
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| Abstract |
Redox regulation of specific cysteines via oxidoreductases of the thioredoxin family is increasingly being recognized as an important signaling pathway. Here, we demonstrate that the cytosolic isoform of the vertebrate-specific oxidoreductase Glutaredoxin 2 (Grx2c) regulates the redox state of the transcription factor SP-1 and thereby its binding affinity to both the promoter and an enhancer region of the CSPG4 gene encoding chondroitin sulfate proteoglycan nerve/glial antigen 2 (NG2). This leads to an increased number of NG2 glia during in vitro oligodendroglial differentiation and promotes migration of these wound healing cells. On the other hand, we found that the same mechanism also leads to increased invasion of glioma tumor cells. Using in vitro (human cell lines), ex vivo (mouse primary cells), and in vivo models (zebrafish), as well as glioblastoma patient tissue samples we provide experimental data highlighting the Yin and Yang of redox signaling in the central nervous system and the enzymatic Taoism of Grx2c.
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| Authors | Christina Wilms, Klaudia Lepka, Felix Häberlein, Steven Edwards, Jörg Felsberg, Linda Pudelko, Tobias T Lindenberg, Gereon Poschmann, Nan Qin, Katrin Volbracht, Tim Prozorovski, Sven G Meuth, Ulf D Kahlert, Marc Remke, Orhan Aktas, Guido Reifenberger, Lars Bräutigam, Benjamin Odermatt, Carsten Berndt |
| Journal | Redox biology (Redox Biol) Vol. 49 Pg. 102221 (02 2022) ISSN: 2213-2317 [Electronic] Netherlands |
| PMID | 34952462 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved. |
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