High mobility group box 1 (HMGB1) is a highly conserved and ubiquitous nuclear protein in eukaryotic cells. In response to stress, it transfers from the nucleus to the cytoplasm and finally, to the extracellular matrix, participating in inflammation and carcinogenesis. Increased HMGB1 protein levels are frequently associated with the reduced survival of patients with glioma. HMGB1 plays contextual roles depending on its subcellular localization. However, the mechanisms underlying its subcellular localization and secretion remain unclear. In the present study, the subcellular localization and secretion of HMGB1 in starved glioma cells were investigated using immunofluorescence microscopy, enzyme‑linked immunosorbent assay, subcellular fractionation, western blotting and immunoelectron microscopy. The results demonstrated that starvation induced HMGB1 translocation from the nucleus to the cytoplasm and finally, to the extracellular milieu in glioma cells. HMGB1 was localized in the mitochondria, endoplasmic reticulum (ER), peroxisomes, autophagosomes, lysosomes, endosomes and the cytoskeleton. Immunoelectron microscopy confirmed that HMGB1 was present within or around cytosolic compartments. Subcellular fractionation further demonstrated that HMGB1 transferred to membrane‑bound compartments. In addition, HMGB1 was localized to specific contact areas between the ER and mitochondria, known as mitochondria‑associated membranes. On the whole, the results of the present study suggest that starvation induces HMGB1 secretion, which can be inhibited through the suppression of autophagy. Starvation insult induces HMGB1 translocation to the cytosolic compartments of glioma cells, and autophagy may be involved in the extracellular secretion of HMGB1 in starved glioma cells.

中文翻译：

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饥饿损伤诱导高迁移率族盒 1 易位至神经胶质瘤中的胞质区室。

高迁移率族蛋白 1 (HMGB1) 是真核细胞中高度保守且普遍存在的核蛋白。为了应对应激，它从细胞核转移到细胞质，最后转移到细胞外基质，参与炎症和癌变。HMGB1 蛋白水平升高通常与神经胶质瘤患者的生存率降低有关。HMGB1 根据其亚细胞定位发挥上下文作用。然而，其亚细胞定位和分泌的机制仍不清楚。在本研究中，利用免疫荧光显微镜、酶联免疫吸附测定、亚细胞分级分离、蛋白质印迹和免疫电镜研究了饥饿胶质瘤细胞中 HMGB1 的亚细胞定位和分泌。结果表明，饥饿诱导神经胶质瘤细胞中 HMGB1 从细胞核易位到细胞质，最后转移到细胞外环境。HMGB1 定位于线粒体、内质网 (ER)、过氧化物酶体、自噬体、溶酶体、内体和细胞骨架。免疫电子显微镜证实 HMGB1 存在于胞质区室内或周围。亚细胞分离进一步证明 HMGB1 转移至膜结合区室。此外，HMGB1 定位于 ER 和线粒体之间的特定接触区域，称为线粒体相关膜。总体而言，本研究结果表明饥饿会诱导 HMGB1 分泌，而这种分泌可以通过抑制自噬来抑制。饥饿损伤诱导 HMGB1 易位至神经胶质瘤细胞的胞质区室，并且自噬可能参与饥饿神经胶质瘤细胞中 HMGB1 的细胞外分泌。