Redox Modulation of HMGB1-Related Signaling
| Autor: | Christine Schorn, Luis E. Muñoz, Martin Herrmann, Milos R. Filipovic, Georg Schett, Ivana Ivanović-Burmazović, Christina Janko |
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| Rok vydání: | 2014 |
| Předmět: |
Physiology
Clinical Biochemistry chemical and pharmacologic phenomena Inflammation HMGB1 Biochemistry Immune tolerance Proinflammatory cytokine Superoxide dismutase chemistry.chemical_compound medicine Animals Humans HMGB1 Protein Molecular Biology General Environmental Science biology Superoxide Cell Biology Forum Review Articles Cell biology chemistry biology.protein Cytokines General Earth and Planetary Sciences Signal transduction medicine.symptom Oxidation-Reduction Peroxynitrite Signal Transduction |
| Zdroj: | Antioxidants & Redox Signaling. 20:1075-1085 |
| ISSN: | 1557-7716 1523-0864 |
| DOI: | 10.1089/ars.2013.5179 |
| Popis: | Significance: In the cells' nuclei, high-mobility group box protein 1 (HMGB1) is a nonhistone chromatin-binding protein involved in the regulation of transcription. Extracellularly, HMGB1 acts as a danger molecule with properties of a proinflammatory cytokine. It can be actively secreted from myeloid cells or passively leak from any type of injured, necrotic cell. Increased serum levels of active HMGB1 are often found in pathogenic inflammatory conditions and correlate with worse prognoses in cancer, sepsis, and autoimmunity. By damaging cells, superoxide and peroxynitrite promote leakage of HMGB1. Recent Advances: The activity of HMGB1 strongly depends on its redox state: Inflammatory-active HMGB1 requires an intramolecular disulfide bond (Cys23 and Cys45) and a reduced Cys106. Oxidation of the latter blocks its stimulatory activity and promotes immune tolerance. Critical Issues: Reactive oxygen and nitrogen species create an oxidative environment and can be detoxified by superoxide dismutase (SOD), catalase, and peroxidases. Modifications of the oxidative environment influence HMGB1 activity. Future Directions: In this review, we hypothesize that manipulations of an oxidative environment by SOD mimics or by hydrogen sulfide are prone to decrease tissue damage. Both the concomitant decreased HMGB1 release and its redox chemical modifications ameliorate inflammation and tissue damage. Antioxid. Redox Signal. 20, 1075–1085. |
| Databáze: | OpenAIRE |
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