Glutaredoxin 2 promotes SP-1-dependent CSPG4 transcription and migration of wound healing NG2 glia and glioma cells: Enzymatic Taoism
| Autor: | 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 |
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| Rok vydání: | 2022 |
| Předmět: |
Medicine (General)
OPCs oligodendrocyte progenitor cells Redox signaling MBP myelin basic protein QH301-705.5 NG2 nerve/glial antigen 2 Clinical Biochemistry Cancer invasion IDH isocitrate dehydrogenase Biochemistry Grx Glutaredoxin Religious Philosophies Mice R5-920 CSPG4 chondroitin sulfate proteoglycan 4 Animals Humans Biology (General) Glutaredoxins Zebrafish Wound Healing Trx Thioredoxin Oligodendrocytes Organic Chemistry Membrane Proteins Glioma PLP proteolipid protein Chondroitin Sulfate Proteoglycans Glioblastoma CNPase 2′ 3′-cyclic nucleotide 3′-phosphodiesterase Neuroglia Transcription Research Paper |
| Zdroj: | Redox Biology Redox Biology, Vol 49, Iss, Pp 102221-(2022) |
| ISSN: | 2213-2317 |
| DOI: | 10.1016/j.redox.2021.102221 |
| Popis: | 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. Graphical abstract Image 1 Highlights • CSPG4 promoter binding of the transcription factor SP-1 depends on glutaredoxin 2 • Cytosolic glutaredoxin 2 promotes oligodendrocyte differentiation into NG2 glia • Migration and wound healing capacity of NG2 glia is increased by glutaredoxin 2 • Glutaredoxin 2 increases invasion of human glioblastoma cells in vitro and in vivo |
| Databáze: | OpenAIRE |
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