Reactive oxygen species (ROS) is an oxidative stress to which cells respond by activating various defense mechanisms or cell death. Autophagy associated with oxidative stress response is a process to degrade and recycle macro-molecule as well as organelles in eukaryotic cells. HMGB1, a ubiquitous nuclear protein, is actively released in eukaryotic cells under oxidative stress. HMGB1 plays an important role as regulator of autophagy in nuclear, cytosolic and extracellular level. Nuclear HMGB1 regulates the expression of heat shock protein beta-1 (HSPB1), which is critical for dynamic intracellular trafficking during autophagy and mitophagy. Cytoplasmic HMGB1 can bind to a beclin 1 by the intramolecular disulfide bridge using cysteine 23 and 45, which dissociates its inhibitory partner Bcl-2 and induces autophagy. Extracellular HMGB1 binds to receptor for advanced glycation endproducts (RAGE) which inhibits mammalian target of rapamycin (mTOR) and then promotes the formation of the belin1-Ptdlns3KC3 complex. Furthermore, endogenous HMGB1 is an intrinsic regulator of autophagy, and it enhances chemoresistance in diverse cancer cells. Here, we review recent reports suggesting a novel mechanism of diverse cancer cell resistance to therapy facilitated by HMGB1-mediated autophagy.
Advanced Glycosylation End Product-Specific Receptor ; Autophagy ; Cell Death ; Cysteine ; Cytoplasm ; Cytosol ; Defense Mechanisms ; Drug Resistance ; Eukaryotic Cells ; HMGB1 Protein ; HSP27 Heat-Shock Proteins ; Mitochondrial Degradation ; Nuclear Proteins ; Organelles ; Oxidative Stress ; Reactive Oxygen Species ; Receptors, Immunologic ; Sirolimus

With growing accounts of inflammatory diseases such as sepsis, greater understanding the immune system and the mechanisms of cellular immunity have become primary objectives in immunology studies. High mobility group box 1 (HMGB1) is a ubiquitous nuclear protein that is implicated in various aspects of the innate immune system as a damage-associated molecular pattern molecule and a late mediator of inflammation, as well as in principal cellular processes, such as autophagy and apoptosis. HMGB1 functions in the nucleus as a DNA chaperone; however, it exhibits cytokine-like activity when secreted by injurious or infectious stimuli. Extracellular HMGB1 acts through specific receptors to promote activation of the NF-kappaB signaling pathway, leading to production of cytokines and chemokines. These findings further implicate HMGB1 in lethal inflammatory diseases as a crucial regulator of inflammatory, injurious, and infectious responses. In this paper, we summarize the role of HMGB1 in inflammatory and non-inflammatory states and assess potential therapeutic approaches targeting HMGB1 in inflammatory diseases.
Amino Acid Sequence ; HMGB1 Protein/chemistry/metabolism/*physiology ; Humans ; Immunity, Innate/*physiology ; *Models, Immunological ; Molecular Sequence Data ; Protein Structure, Tertiary ; Signal Transduction

PURPOSE:The purpose of this study is to evaluate the change of pancreatic size after gastric resection in patients with gastric malignancy. MATERIALS AND METHODS: We compared the pancreatic sizes on pre- and post-operative abdominal CT scans in 50 patients whose stomach had been resected due to malignancy. The mean interval was 20.3 months (range, 5-81 months). The types of the operation were total gastrectomy with esophagojejunostomy and jejunojejunostomy (n=7), and subtotal gastrectomy with gastrojejunostomy (Billroth II) (n=43). Pancreatic thickness was measured perpendicular to the pancreatic long axis at head, body and tail. RESULT: There was a significant reduction of pancreatic size on postoperative CT scan. The reduction rate was 5.9% in the head (p<0.001), 7.1% in the body (p<0.001) and 14.4% in the tail (p<0.001). CONCLUSION:Significant reduction of pancreatic size was observed after gastric resection due to gastric rnalignancy, especially in tail.
Axis, Cervical Vertebra ; Gastrectomy ; Gastric Bypass ; Head ; Humans ; Stomach ; Tomography, X-Ray Computed

Peroxiredoxins (Prxs) are ubiquitously expressed peroxidases that reduce hydrogen peroxide or alkyl peroxide production in cells. Prxs are released from cells in response to various stress conditions, and they function as damage-associated molecular pattern molecules. However, the secretory mechanism of Prxs and their roles have not been elucidated. Thus, we aimed to determine whether inflammasome activation is a secretory mechanism of Prxs and subsequently identify the effect of the secreted Prxs on activation of the classical complement pathway. Using J774A.1, a murine macrophage cell line, we demonstrated that NLRP3 inflammasome activation induces Prx1, Prx2, Prx5, and Prx6 secretion in a caspase-1 dependent manner. Using HEK293T cells with a transfection system, we revealed that the release of Prx1 and Prx2 relies on gasdermin-D (GSDMD)-mediated secretion. Next, we confirmed the binding of both Prx1 and Prx2 to C1q; however, only Prx2 could induce the C1q-mediated classical complement pathway activation. Collectively, our results suggest that inflammasome activation is a secretory mechanism of Prxs and that GSDMD is a mediator of their secretion. Moreover, secreted Prx1 and Prx2 bind with C1q, but only Prx2 mediates the classical complement pathway activation.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces excessive pro-inflammatory cytokine release and cell death, leading to organ damage and mortality.High-mobility group box 1 (HMGB1) is one of the damage-associated molecular patterns that can be secreted by pro-inflammatory stimuli, including viral infections, and its excessive secretion levels are related to a variety of inflammatory diseases. Here, the aim of the study was to show that SARS-CoV-2 infection induced HMGB1 secretion via active and passive release. Active HMGB1 secretion was mediated by post-translational modifications, such as acetylation, phosphorylation, and oxidation in HEK293E/ACE2-C-GFP and Calu-3 cells during SARS-CoV-2 infection. Passive release of HMGB1 has been linked to various types of cell death; however, we demonstrated for the first time that PANoptosis, which integrates other cell death pathways, including pyroptosis, apoptosis, and necroptosis, is related to passive HMGB1 release during SARS-CoV-2 infection. In addition, cytoplasmic translocation and extracellular secretion or release of HMGB1 were confirmed via immunohistochemistry and immunofluorescence in the lung tissues of humans and angiotensin-converting enzyme 2-overexpressing mice infected with SARS-CoV-2.