Glutaredoxin 2 promotes SP-1-dependent CSPG4 transcription and migration of wound healing NG2 glia and glioma cells: Enzymatic Taoism
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
Affiliations
Christina Wilms
Department of Neurology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Germany
Klaudia Lepka
Department of Neurology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Germany
Felix Häberlein
Institute for Anatomy, Medical Faculty, University Bonn, Germany
Steven Edwards
SciLifeLab, Karolinska Institute, Stockholm, Sweden
Jörg Felsberg
Institute of Neuropathology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Germany
Linda Pudelko
Zebrafish Core Facility, Karolinska Institute, Stockholm, Sweden
Tobias T. Lindenberg
Institute for Anatomy, Medical Faculty, University Bonn, Germany
Gereon Poschmann
Institute of Molecular Medicine, Proteome Research, Medical Faculty and University Hospital Düsseldorf, HeinrichHeineUniversity Düsseldorf, Germany
Nan Qin
Department of Pediatric Oncology, Hematology and Clinical Immunology, Pediatric Neuro-Oncogenomics, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Germany
Katrin Volbracht
Department of Neurology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Germany
Tim Prozorovski
Department of Neurology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Germany
Sven G. Meuth
Department of Neurology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Germany
Ulf D. Kahlert
Molecular and Experimental Surgery, University Clinic for General, Visceral and Vascular Surgery, Otto-von-Guericke-University Magdeburg, Germany
Marc Remke
Department of Pediatric Oncology, Hematology and Clinical Immunology, Pediatric Neuro-Oncogenomics, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Germany
Orhan Aktas
Department of Neurology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Germany
Guido Reifenberger
Institute of Neuropathology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Germany
Lars Bräutigam
Zebrafish Core Facility, Karolinska Institute, Stockholm, Sweden
Benjamin Odermatt
Institute for Anatomy, Medical Faculty, University Bonn, Germany
Carsten Berndt
Department of Neurology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Germany; Corresponding author. Department of Neurology, Medical Faculty, Heinrich Heine University Düsseldorf, Life Science Center, Merowingerplatz 1a, 40225, Düsseldorf, Germany.
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.
