1 Department of Internal Medicine 3, Rheumatology and Immunology, Friedrich-Alexander-University of Erlangen-Nuremberg , Erlangen, Germany .
Antioxid Redox Signal. 2014 Mar 1;20(7):1075-85. doi: 10.1089/ars.2013.5179. Epub 2013 Mar 19.
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.
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.
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.
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.
在细胞的细胞核中，高迁移率族蛋白 B1（HMGB1）是一种非组蛋白染色质结合蛋白，参与转录的调节。细胞外，HMGB1 作为一种危险分子，具有前炎性细胞因子的特性。它可以从髓样细胞中主动分泌，也可以从任何类型的受损、坏死细胞中被动渗漏。活性 HMGB1 的血清水平升高通常见于致病炎症状态，并与癌症、败血症和自身免疫中的预后不良相关。超氧阴离子和过氧亚硝酸盐通过破坏细胞促进 HMGB1 的渗漏。
HMGB1 的活性强烈依赖于其氧化还原状态：炎症激活的 HMGB1 需要一个分子内二硫键（Cys23 和 Cys45）和一个还原的 Cys106。后者的氧化会阻止其刺激活性并促进免疫耐受。
活性氧和氮物种会产生氧化环境，并可被超氧化物歧化酶（SOD）、过氧化氢酶和过氧化物酶解毒。氧化环境的改变会影响 HMGB1 的活性。
在这篇综述中，我们假设 SOD 模拟物或硫化氢对氧化环境的操纵可能会减少组织损伤。HMGB1 释放的减少及其氧化还原化学修饰的同时改善炎症和组织损伤。
