High Mobility Group Box 1 (HMGB1) Activates an Autophagic Response to Oxidative Stress

Advanced glycation end products (AGEs) are produced in response to a high-glucose environment and oxidative stress and exacerbate various diseases. Nε-(Carboxymethyl)lysine (CML) is an AGE that is produced by the glycation of lysine residues of proteins. There are a few reports on alterations in protein function due to CML modification; however, its association with cancer is not clear. We investigated the significance of CML modification in high mobility group box protein-1 (HMGB1), a cytokine that is significantly associated with cancer progression. Treatment of the gastric cancer cell lines TMK1 and MKN74 with glyoxal or glucose resulted in increased CML modification compared to untreated cells. CML-HMGB1 was modified via oxidation and more pronouncedly activated the receptor for AGE and downstream AKT and NF-κB compared to naïve HMGB1 and oxidized HMGB1. CML-HMGB1 bound with reduced affinity to DNA and histone H3, resulting in enhanced extranuclear translocation and extracellular secretion. Treatment of gastric cancer cells with CML-HMGB1 enhanced cell proliferation and invasion, sphere formation, and protection from thapsigargin-induced apoptosis, and decreased 5-FU sensitivity in comparison to HMGB1. Further, CML-HMGB1 was detected at various levels in all the 10 gastric cancer tumor specimens. HMGB1 levels correlated with primary tumor progression and distant metastasis, whereas CML-HMGB1 levels were associated with primary tumor progression, lymph node metastasis, distant metastasis, and stage. In addition, CML-HMGB1 levels correlated with oxidative stress in cancer tissues and resistance to neoadjuvant therapy. Therefore, CML modification of HMGB1 enhanced the cancer-promoting effect of HMGB1. In this study, CML-HMGB1 has been highlighted as a new therapeutic target, and analysis of the molecular structure of CML-HMGB1 is desired in the future.

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Diabetes-Induced Oxidative Stress in Endothelial Progenitor Cells May Be Sustained by a Positive Feedback Loop Involving High Mobility Group Box-1

Oxidative Medicine and Cellular Longevity ◽

10.1155/2016/1943918 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 13

Author(s):

Han Wu ◽

Ran Li ◽

Zhong-Hai Wei ◽

Xin-Lin Zhang ◽

Jian-Zhou Chen ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Culture ◽

Positive Feedback ◽

Feedback Loop ◽

High Mobility ◽

High Mobility Group ◽

Dependent Manner ◽

Endothelial Progenitor ◽

Positive Feedback Loop ◽

Culture Supernatants

Oxidative stress is considered to be a critical factor in diabetes-induced endothelial progenitor cell (EPC) dysfunction, although the underlying mechanisms are not fully understood. In this study, we investigated the role of high mobility group box-1 (HMGB-1) in diabetes-induced oxidative stress. HMGB-1 was upregulated in both serum and bone marrow-derived monocytes from diabetic mice compared with control mice. In vitro, advanced glycation end productions (AGEs) induced, expression of HMGB-1 in EPCs and in cell culture supernatants in a dose-dependent manner. However, inhibition of oxidative stress with N-acetylcysteine (NAC) partially inhibited the induction of HMGB-1 induced by AGEs. Furthermore, p66shc expression in EPCs induced by AGEs was abrogated by incubation with glycyrrhizin (Gly), while increased superoxide dismutase (SOD) activity in cell culture supernatants was observed in the Gly treated group. Thus, HMGB-1 may play an important role in diabetes-induced oxidative stress in EPCs via a positive feedback loop involving the AGE/reactive oxygen species/HMGB-1 pathway.

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The Effect of Ethyl Pyruvate on High Mobility Group Box I and Oxidative Stress in Induced Rheumatoid Arthritis in Rats

The Medical Journal of Cairo University ◽

10.21608/mjcu.2019.54867 ◽

2019 ◽

Vol 87 (June) ◽

pp. 2547-2554

Author(s):

HADEER S. SALAH, M.Sc. OMNIA S. EL-DEEB, M.D. ◽

SAAD EL-DEEN A. ABO EL-NOEMAN, M.D NAGAH K. GAAFAR, M.D.

Keyword(s):

Rheumatoid Arthritis ◽

Oxidative Stress ◽

Ethyl Pyruvate ◽

High Mobility ◽

High Mobility Group ◽

And Oxidative Stress

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Relationship between the use of polymyxin B-immobilized fiber for hemofiltration and some laboratory parameters (endocannabinoids, high mobility group box-1 protein and oxidative stress) in severe pneumonia patients

Critical Care ◽

10.1186/cc6677 ◽

2008 ◽

Vol 12 (Suppl 2) ◽

pp. P456

Author(s):

K Mashiko ◽

Y Sakamoto ◽

T Obata ◽

H Matsumoto ◽

Y Hara ◽

...

Keyword(s):

Oxidative Stress ◽

High Mobility ◽

Severe Pneumonia ◽

Polymyxin B ◽

High Mobility Group ◽

Laboratory Parameters ◽

And Oxidative Stress

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High Mobility Group B Proteins, Their Partners, and Other Redox Sensors in Ovarian and Prostate Cancer

Oxidative Medicine and Cellular Longevity ◽

10.1155/2016/5845061 ◽

2016 ◽

Vol 2016 ◽

pp. 1-17 ◽

Cited By ~ 17

Author(s):

Aida Barreiro-Alonso ◽

Mónica Lamas-Maceiras ◽

Esther Rodríguez-Belmonte ◽

Ángel Vizoso-Vázquez ◽

María Quindós ◽

...

Keyword(s):

Oxidative Stress ◽

Prostate Cancer ◽

Structural Changes ◽

Molecular Mechanisms ◽

High Mobility ◽

High Mobility Group ◽

Redox Sensor ◽

Group B ◽

Different Origins ◽

Hmgb Proteins

Cancer cells try to avoid the overproduction of reactive oxygen species by metabolic rearrangements. These cells also develop specific strategies to increase ROS resistance and to express the enzymatic activities necessary for ROS detoxification. Oxidative stress produces DNA damage and also induces responses, which could help the cell to restore the initial equilibrium. But if this is not possible, oxidative stress finally activates signals that will lead to cell death. High mobility group B (HMGB) proteins have been previously related to the onset and progressions of cancers of different origins. The protein HMGB1 behaves as a redox sensor and its structural changes, which are conditioned by the oxidative environment, are associated with different functions of the protein. This review describes recent advances in the role of human HMGB proteins and other proteins interacting with them, in cancerous processes related to oxidative stress, with special reference to ovarian and prostate cancer. Their participation in the molecular mechanisms of resistance to cisplatin, a drug commonly used in chemotherapy, is also revised.

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MiR-582-5p attenuates neonatal hypoxic-ischemic encephalopathy by targeting high mobility group box 1 (HMGB1) through inhibiting neuroinflammation and oxidative stress

Current Neurovascular Research ◽

10.2174/1567202618666211109102740 ◽

2021 ◽

Vol 18 ◽

Author(s):

Guang Yang ◽

Zhimin Xue ◽

Yuan Zhao

Keyword(s):

Oxidative Stress ◽

Cell Viability ◽

Pc12 Cells ◽

Pc12 Cell ◽

Cell Injury ◽

High Mobility ◽

High Mobility Group ◽

Hypoxic Ischemic Encephalopathy ◽

And Oxidative Stress ◽

Ischemic Encephalopathy

Background: MiR-582-5p has been demonstrated to protect against ischemic stroke. However, its implication in the progression of neonatal hypoxic-ischemic encephalopathy (HIE) has not been explored. Methods: In this study, we used an in vitro model of oxygen-glucose deprivation (OGD) to investigate the protective effect of miR-582-5p on PC12 cells. OGD-induced inhibition of cell viability and promotion of cell death was assessed by CCK-8 assay and flow cytometry. Real-time PCR and enzyme-linked immunosorbent assay (ELISA) were utilized to examine the levels of inflammatory cytokines. The effects of miR-582-5p on OGD-induced oxidative injury were assessed by the determination of oxidative stress indicators. Furthermore, dual-luciferase reporter assay and gain-offunction assay were used to determine the mechanism of miR-582-5p in OGD-induced cell injury. Results : The expression of miR-582-5p was reduced upon OGD treatment in PC12 cells. Overexpression of miR-582-5p inhibited OGD-induced PC12 cell injury by regulating cell viability, apoptosis, inflammatory responses, and oxidative stress. MiR-582-5p targeted and negatively regulated high mobility group box 1 (HMGB1). MiR-582-5p presented protective effects on OGD-induced PC12 cell injury by targeting HMGB1. Conclusion: Our results indicated that miR-582-5p ameliorates neuronal injury by inhibiting apoptosis, inflammation, and oxidative stress through targeting HMGB1.

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