High-Mobility Group Protein Box-1 and its Relevance to Cerebral Ischemia

High-mobility group box-1 (HMGB1) was originally identified as a ubiquitously expressed, abundant, nonhistone DNA-binding protein. It has well-established functions in the maintenance of nuclear homeostasis. The HMGB1 can either be passively released into the extracellular milieu in response to necrotic signals or actively secreted in response to inflammatory signals. Extracellular HMGB1 interacts with receptors, including those for advanced glycation endproducts (RAGEs) as well as Toll-like receptor 2 (TLR2) and TLR4. The HMGB1 functions in a synergistic manner with other proinflammatory mediators and acts as a potent proinflammatory cytokine-like factor that contributes to the pathogenesis of diverse inflammatory and infectious disorders. Numerous reports point to HMGB1 as a novel player in the ischemic brain. This review provides an appraisal of the emerging roles of HMGB1 in cerebral ischemia injury, highlighting the relevance of HMGB1-blocking agents as potent therapeutic tools for neuroprotection.

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Heparin changes the conformation of high-mobility group protein 1 and decreases its affinity toward receptor for advanced glycation endproducts in vitro

International Immunopharmacology ◽

10.1016/j.intimp.2010.11.014 ◽

2011 ◽

Vol 11 (2) ◽

pp. 187-193 ◽

Cited By ~ 25

Author(s):

Yan Ling ◽

Zhi-Yong Yang ◽

Tao Yin ◽

Li Li ◽

Wei-Wei Yuan ◽

...

Keyword(s):

Advanced Glycation Endproducts ◽

High Mobility ◽

High Mobility Group ◽

Advanced Glycation ◽

High Mobility Group Protein ◽

Glycation Endproducts ◽

Group Protein

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Abstract TP167: Suppression of High-mobility Group Protein Box-1 Signaling by Eicosapentaenoic Acid Ameliorates Brain Ischemic Damage in Oophorectomized Rats

Stroke ◽

10.1161/str.44.suppl_1.atp167 ◽

2013 ◽

Vol 44 (suppl_1) ◽

Author(s):

Manabu Sumiyoshi ◽

Keiko T Kitazato ◽

Kenji Yagi ◽

Kenji Shimada ◽

Nobuhisa Matsushita ◽

...

Keyword(s):

Cerebral Ischemia ◽

Eicosapentaenoic Acid ◽

Infarct Size ◽

Brain Damage ◽

High Mobility ◽

High Mobility Group ◽

Female Rats ◽

Male Rats ◽

High Mobility Group Protein ◽

Group Protein

Background and Purpose— Cerebral ischemia triggers the acute inflammation that has been associated with an increase in brain damage. In male rats exposed to ischemic insult, high-mobility group protein box-1 (HMGB1) activates inflammatory pathways via its receptor for advanced glycation products (RAGE) and its toll-like receptors (TLRs). We examined the role of these molecules in female rats with experimental ischemic brain damage. We further investigated the efficacy of eicosapentaenoic acid (EPA) against cerebral ischemia and its effect on HMGB1 signaling. Methods— Before 90-min middle cerebral artery occlusion-reperfusion, 5-week-old female Sprague-Dawley rats were subjected to bilateral oophorectomy (OVX + ) and pretreated with 500mg/kg/day EPA for 4 weeks. The relationship between the efficacy of EPA and the regulation of HMGB1 signaling were investigated using peroxisome proliferator-activated receptor gamma (PPARγ) agonist pioglitazone, PPARγ inhibitor GW9662, and vehicle-control. Results— In parallel with the expansion of the cortical infarct size, HMGB1 signaling after cerebral ischemia was increased in OVX + rats. The mRNA level of TLR9 and RAGE but not TLR2 and TLR4 was moderately increased by cerebral ischemia and significantly higher in OVX + - than OVX - rats. The HMGB1 signal in the OVX + rats pretreated with EPA was inhibited in a PPARγ-dependent and independent manner. These effects were associated with a reduction in the infarct size. Conclusions— We first demonstrate that cortical infarct facilitated by OVX is associated with augmented HMGB1 signaling and that the augmented HMGB1 signaling was suppressed by EPA. To assess whether EPA treatment is a promising strategy further clinical studies are required in postmenopausal women.

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High Mobility Group Protein HMG-R

10.32388/nb6yys ◽

2020 ◽

Author(s):

Keyword(s):

High Mobility ◽

High Mobility Group ◽

High Mobility Group Protein ◽

Group Protein

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Faculty Opinions recommendation of Actively transcribed rRNA genes in S. cerevisiae are organized in a specialized chromatin associated with the high-mobility group protein Hmo1 and are largely devoid of histone molecules.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1144960.602064 ◽

2009 ◽

Author(s):

Jim Maher

Keyword(s):

High Mobility ◽

High Mobility Group ◽

Rrna Genes ◽

High Mobility Group Protein ◽

Group Protein

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The Immune Tolerance Role of the HMGB1-RAGE Axis

Cells ◽

10.3390/cells10030564 ◽

2021 ◽

Vol 10 (3) ◽

pp. 564

Author(s):

Haruki Watanabe ◽

Myoungsun Son

Keyword(s):

Immune Responses ◽

Immune Tolerance ◽

Lupus Erythematosus ◽

Advanced Glycation Endproducts ◽

High Mobility ◽

Chromatin Binding ◽

Advanced Glycation ◽

Glycation Endproducts ◽

Extracellular Milieu

The disruption of the immune tolerance induces autoimmunity such as systemic lupus erythematosus and vasculitis. A chromatin-binding non-histone protein, high mobility group box 1 (HMGB1), is released from the nucleus to the extracellular milieu in particular environments such as autoimmunity, sepsis and hypoxia. Extracellular HMGB1 engages pattern recognition receptors, including Toll-like receptors (TLRs) and the receptor for advanced glycation endproducts (RAGE). While the HMGB1-RAGE axis drives inflammation in various diseases, recent studies also focus on the anti-inflammatory effects of HMGB1 and RAGE. This review discusses current perspectives on HMGB1 and RAGE’s roles in controlling inflammation and immune tolerance. We also suggest how RAGE heterodimers responding microenvironments functions in immune responses.

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