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HMGB1的不同氧化还原形式及其临床意义
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 HMGB1的不同氧化还原形式及其临床意义
杨珺,罗海华,姜勇
基金项目:高等学校博士学科点专项科研基金(No.20104433110008),国家自然科学基金(No.81030055),广东省自然科学基金项目(No.S2013010014422)。 作者简介:杨珺(1988),女,八年制临床医学专业学生,从亊炎症细胞信号转导方面的研究 通信联系人:姜勇(1964),男,教授,博士生导师,长期从事炎症的细胞信号转导研究.

(广州南方医科大学病理生理学教研室暨广东省蛋白质组学重点实验室,广州 510515)

摘要:HMGB1是HMG超家族中的一员,是一种具有胞外炎症细胞因子活性对氧化还原敏感的核蛋白,它可由损伤或坏死细胞被动释放,也可被免疫细胞主动释放到胞外。不同状态的HMGB1介导的受损组织的炎症细胞募集,细胞因子诱导的过程,需要不同的受体。二硫键型HMGB1通过与TLR4受体的相互作用来促进细胞因子的释放;而硫醇型HMGB1与趋化因子CXCL12形成异源复合物,再与CXCR4特异性结合;还原型HMGB1与RAGE结合,促进Beclin1依赖的自噬;氧化型HMGB1通过caspase-9/3内源性通路诱导凋亡。HMGB1的重要性使其成为一个治疗性干预的靶点,理解氧化应激过程中HMGB1及其复杂的功能成为减少氧化损伤的新策略,尤其在慢性炎症以及癌症中更应重视。
关键词:HMGB1;氧化还原;自噬;炎症;免疫
中图分类号:R392.9
The different redox forms of HMGB1 and their clinical significancy
YANG Jun, LUO Haihua, JIANGYong
(Department of Pathophysiology, Key Laboratory of Proteomics of Gongdong Province, Southern Medical University, Guangzhou 510515)
Abstract: High mobility group box 1 (HMGB1) is a member of HMG family, as well as a nuclear protein with extracellular inflammatory cytokine activity. It is released passively during cell injury and necrosis, and secreted actively by immune cells. The recruitment of inflammatory cells to damaged tissues and the induction of cytokines by different forms of HMGB1 involve different receptors. Disulfide HMGB1 promotes cytokine release via its interaction with the TLR4, whereas thiol HMGB1 forms a heterocomplex with the chemokine CXCL12 that acts exclusively via CXCR4. Reduced HMGB1 binds to RAGE, thus promoting Beclin1-dependent autophagy. Oxidized HMGB1 induces apoptosis via a Caspase-9/3 intrinsic pathway. Therefore, HMGB1 may be qualified as a target for therapeutic interventions. Understanding the effects of HMGB1 and its complex in the setting of oxidative stress may lead to the development of novel strategies to attenuate oxidative injury in various clinical situations, particularly those associated with chronic inflammation, including cancer.
Key words: HMGB1; redox; autophagy; inflammation; immunity