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HMGB1的不同氧化還原形式及其臨床意義
來源: | 作者: | 發布時間:2014-4-15 16:33:45

 HMGB1的不同氧化還原形式及其臨床意義
楊珺,羅海華,姜勇
基金項目:高等學校博士學科點專項科研基金(No.20104433110008),國家自然科學基金(No.81030055),廣東省自然科學基金項目(No.S2013010014422)。 作者簡介:楊珺(1988),女,八年制臨床醫學專業學生,從亊炎癥細胞信號轉導方面的研究 通信聯系人:姜勇(1964),男,教授,博士生導師,長期從事炎癥的細胞信號轉導研究.

(廣州南方醫科大學病理生理學教研室暨廣東省蛋白質組學重點實驗室,廣州 510515)

摘要:HMGB1是HMG超家族中的一員,是一種具有胞外炎癥細胞因子活性對氧化還原敏感的核蛋白,它可由損傷或壞死細胞被動釋放,也可被免疫細胞主動釋放到胞外。不同狀態的HMGB1介導的受損組織的炎癥細胞募集,細胞因子誘導的過程,需要不同的受體。二硫鍵型HMGB1通過與TLR4受體的相互作用來促進細胞因子的釋放;而硫醇型HMGB1與趨化因子CXCL12形成異源復合物,再與CXCR4特異性結合;還原型HMGB1與RAGE結合,促進Beclin1依賴的自噬;氧化型HMGB1通過caspase-9/3內源性通路誘導凋亡。HMGB1的重要性使其成為一個治療性干預的靶點,理解氧化應激過程中HMGB1及其復雜的功能成為減少氧化損傷的新策略,尤其在慢性炎癥以及癌癥中更應重視。
關鍵詞:HMGB1;氧化還原;自噬;炎癥;免疫
中圖分類號: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

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