DAMP Laboratory, Department of Surgery, Hillman Cancer Center, University of Pittsburgh Cancer Institute, University of Pittsburgh, PA, USA.
Autophagy. 2011 Aug;7(8):904-6. doi: 10.4161/auto.7.8.15704. Epub 2011 Aug 1.
High mobility group box 1 (HMGB1) is a DNA-binding nuclear protein, actively released following cytokine stimulation as well as passively during cell injury and death. Autophagy is a tightly regulated cellular stress pathway involving the lysosomal degradation of cytoplasmic organelles or proteins. Organisms respond to oxidative injury by orchestrating stress responses such as autophagy to prevent further damage. Recently, we reported that HMGB1 is an autophagy sensor in the presence of oxidative stress. Hydrogen peroxide (H 2O 2) and loss of superoxide dismutase 1 (SOD1)-mediated oxidative stress promotes cytosolic HMGB1 expression and extracellular release. Inhibition of HMGB1 release or loss of HMGB1 decreases the number of autolysosomes and autophagic flux in human and mouse cell lines under conditions of oxidative stress. These findings provide insight into how HMGB1, a damage associated molecular pattern (DAMP), triggers autophagy as defense mechanism under conditions of cellular stress.
高迁移率族蛋白 B1（HMGB1）是一种 DNA 结合核蛋白，在细胞因子刺激后以及在细胞损伤和死亡过程中会被动释放。自噬是一种受严格调控的细胞应激途径，涉及溶酶体对细胞质细胞器或蛋白质的降解。生物通过协调自噬等应激反应来应对氧化损伤，以防止进一步的损伤。最近，我们报道 HMGB1 是氧化应激条件下的自噬传感器。过氧化氢（H 2O 2）和超氧化物歧化酶 1（SOD1）介导的氧化应激促进细胞溶质 HMGB1 的表达和细胞外释放。在氧化应激条件下，抑制 HMGB1 释放或缺失 HMGB1 会减少人源和鼠源细胞系中自噬溶酶体和自噬流的数量。这些发现提供了深入了解 HMGB1（一种损伤相关分子模式（DAMP））如何在细胞应激条件下作为防御机制触发自噬的机制。
