HMGB1, neuronal excitability and epilepsy

AbstractEpilepsy is a common neurological disease caused by synchronous firing of hyperexcitable neurons. Currently, anti-epileptic drugs remain the main choice to control seizure, but 30% of patients are resistant to the drugs, which calls for more research on new promising targets. Neuroinflammation is closely associated with the development of epilepsy. As an important inflammatory factor, high mobility group protein B1 (HMGB1) has shown elevated expression and an increased proportion of translocation from the nucleus to the cytoplasm in patients with epilepsy and in multiple animal models of epilepsy. HMGB1 can act on downstream receptors such as Toll-like receptor 4 and receptor for advanced glycation end products, thereby activating interleukin (IL)-1β and nuclear factor kappa-B (NF-κB), which in turn act with glutamate receptors such as the N-methyl-D-aspartate (NMDA) receptors to aggravate hyperexcitability and epilepsy. The hyperexcitability can in turn stimulate the expression and translocation of HMGB1. Blocking HMGB1 and its downstream signaling pathways may be a direction for antiepileptic drug therapy. Here, we review the changes of HMGB1-related pathway in epileptic brains and its role in the modulation of neuronal excitability and epileptic seizure. Furthermore, we discuss the potentials of HMGB1 as a therapeutic target for epilepsy and provide perspective on future research on the role of HMGB1 signaling in epilepsy.

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High Mobility Group Protein 1 Reverses Immune System Paralysis in Late-Phase Sepsis

Infection and Immunity ◽

10.1128/iai.00455-18 ◽

2018 ◽

Vol 86 (9) ◽

Author(s):

Qing-yang Liu ◽

Yue-Xin Wang ◽

Zong-Sheng Wu ◽

Zhen-wei Shi ◽

Xu Wu ◽

...

Keyword(s):

Immune Cells ◽

Bone Marrow Cells ◽

Late Phase ◽

Cecal Ligation ◽

High Mobility ◽

High Mobility Group ◽

Infection Model ◽

Inflammatory Factor ◽

High Mobility Group Protein ◽

Group Protein

ABSTRACTHigh mobility group protein 1 (HMGB1) is considered to be the primary inflammatory factor triggering immune paralysis in late-phase sepsis. In this study, however, we wanted to explore the possibility of using HMGB1 to boost local differentiation of bone marrow cells (BMCs) into regulatory dendritic cells (DCs)in vivo, thereby inducing immune reversal in late-phase sepsis and improving the prognosis. For this purpose, sepsis was induced by cecal ligation and puncture (CLP). Mice were injected intraperitoneally with HMGB1 (10, 50, or 250 μg/kg of body weight) 7 days before CLP. BMCs and liver immune cells were isolated at 0, 3, 5, and 7 days post-CLP. Mice were intranasally infected withPseudomonas aeruginosa3 days post-CLP as a secondary pneumonia infection model. BMCs and liver cells isolated from septic mice pretreated with HMGB1 were adoptively transferred into CLP mice. GFP+-C57BL/6 and C3H/HeN-C3H/HeJ parabiosis models were established. We found that HMGB1 pretreatment improved the survival of sepsis and increased the numbers of BMCs and liver immune cells in CLP mice. Furthermore, HMGB1 stimulation improved survival in the secondary pneumonia infection model. HMGB1 increased the number as well as the percentage of CD11c−CD45RBhighDCs in septic BM and liver. Adoptive transfer of septic cells pretreated with HMGB1 into CLP mice attenuated sepsis. HMGB1 enhanced the redistribution of CD11c−CD45RBhighDCs through TLR4 signaling in parabiosis models. We conclude that HMGB1 triggers immune reversal through the mobilization, redistribution, and local immune differentiation of BMCs, thereby compensating for impaired immunity and leading to sufficient bacterial eradication.

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Dieckol Attenuated Glucocorticoid-Induced Muscle Atrophy by Decreasing NLRP3 Inflammasome and Pyroptosis

International Journal of Molecular Sciences ◽

10.3390/ijms22158057 ◽

2021 ◽

Vol 22 (15) ◽

pp. 8057

Author(s):

Seyeon Oh ◽

Jinyoung Yang ◽

Chulhyun Park ◽

Kukhui Son ◽

Kyunghee Byun

Keyword(s):

Muscle Atrophy ◽

Nlrp3 Inflammasome ◽

High Mobility ◽

Nuclear Factor Κb ◽

High Mobility Group Protein ◽

Cross Sectional ◽

Downstream Signaling ◽

Pyrin Domain ◽

Inflammasome Component ◽

Group Protein

Dexamethasone (Dexa), frequently used as an anti-inflammatory agent, paradoxically leads to muscle inflammation and muscle atrophy. Receptor for advanced glycation end products (RAGE) and Toll-like receptor 4 (TLR4) lead to nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3) inflammasome formation through nuclear factor-κB (NF-κB) upregulation. NLRP3 inflammasome results in pyroptosis and is associated with the Murf-1 and atrogin-1 upregulation involved in protein degradation and muscle atrophy. The effects of Ecklonia cava extract (ECE) and dieckol (DK) on attenuating Dexa-induced muscle atrophy were evaluated by decreasing NLRP3 inflammasome formation in the muscles of Dexa-treated animals. The binding of AGE or high mobility group protein 1 to RAGE or TLR4 was increased by Dexa but significantly decreased by ECE or DK. The downstream signaling pathways of RAGE (c-Jun N-terminal kinase or p38) were increased by Dexa but decreased by ECE or DK. NF-κB, downstream of RAGE or TLR4, was increased by Dexa but decreased by ECE or DK. The NLRP3 inflammasome component (NLRP3 and apoptosis-associated speck-like), cleaved caspase -1, and cleaved gasdermin D, markers of pyroptosis, were increased by Dexa but decreased by ECE and DK. Interleukin-1β/Murf-1/atrogin-1 expression was increased by Dexa but restored by ECE or DK. The mean muscle fiber cross-sectional area and grip strength were decreased by Dexa but restored by ECE or DK. In conclusion, ECE or DK attenuated Dexa-induced muscle atrophy by decreasing NLRP3 inflammasome formation and pyroptosis.

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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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HMGA1 Is a Potential Driver of Preeclampsia Pathogenesis by Interference with Extravillous Trophoblasts Invasion

Biomolecules ◽

10.3390/biom11060822 ◽

2021 ◽

Vol 11 (6) ◽

pp. 822

Author(s):

Keiichi Matsubara ◽

Yuko Matsubara ◽

Yuka Uchikura ◽

Katsuko Takagi ◽

Akiko Yano ◽

...

Keyword(s):

Protein A ◽

High Mobility ◽

Extravillous Trophoblast ◽

High Mobility Group Protein ◽

Successful Pregnancy ◽

Group Protein ◽

Serious Disease ◽

Proliferation And Invasion ◽

Extravillous Trophoblasts ◽

Fertilized Egg

Preeclampsia (PE) is a serious disease that can be fatal for the mother and fetus. The two-stage theory has been proposed as its cause, with the first stage comprising poor placentation associated with the failure of fertilized egg implantation. Successful implantation and placentation require maternal immunotolerance of the fertilized egg as a semi-allograft and appropriate extravillous trophoblast (EVT) invasion of the decidua and myometrium. The disturbance of EVT invasion during implantation in PE results in impaired spiral artery remodeling. PE is thought to be caused by hypoxia during remodeling failure–derived poor placentation, which results in chronic inflammation. High-mobility group protein A (HMGA) is involved in the growth and invasion of cancer cells and likely in the growth and invasion of trophoblasts. Its mechanism of action is associated with immunotolerance. Thus, HMGA is thought to play a pivotal role in successful pregnancy, and its dysfunction may be related to the pathogenesis of PE. The evaluation of HMGA function and its changes in PE might confirm that it is a reliable biomarker of PE and provide prospects for PE treatment through the induction of EVT proliferation and invasion during the implantation.

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