LPS-induced histone H3 phospho(Ser10)-acetylation(Lys14) regulates neuronal and microglial neuroinflammatory response

Rigillo, Giovanna; Vilella, Antonietta; Benatti, Cristina; Schaeffer, Laurent; Brunello, Nicoletta; Blom, Johanna Maria Catharina; Zoli, Michèle; Tascedda, Fabio

doi:10.1016/j.bbi.2018.09.019

Cited by 39 publications

(24 citation statements)

References 98 publications

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“…Whether the inflammation mediates OEG damage via Bax-dependent mitochondrial apoptosis is incompletely understood. Previous studies have used LPS to induce the neuroinflammatory (Rigillo et al 2018) and found that LPS could cause mitochondrial damage in the axons (Errea et al 2015), microglia (Ho et al 2018), and spiral ganglion neurons (Zuo et al 2015). Based on these reports, we posited and analyzed the following three hypotheses: (1) whether LPS-induced inflammation caused apoptosis in OEG, (2) whether mitochondrial dysfunction was required for LPS-mediated OEG death, and (3) whether LPS modulated OEG viability and mitochondrial homeostasis via the JNK-Bnip3-Bax signaling pathways.…”

Section: Introductionmentioning

confidence: 99%

Lipopolysaccharide induces human olfactory ensheathing glial apoptosis by promoting mitochondrial dysfunction and activating the JNK-Bnip3-Bax pathway

Xiang

et al. 2019

Cell Stress and Chaperones

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Olfactory ensheathing glia (OEG) play an important role in regulating the regeneration of an injured nervous system. However, chronic inflammation damage reduces the viability of OEG via poorly understood mechanisms. We aimed to investigate the pathological responses of OEG in response to LPS-mediated inflammation stress in vitro. The results indicated that lipopolysaccharide (LPS) treatment significantly reduced the viability of OEG in a dose-dependent fashion. Mechanistically, LPS stimuli induced mitochondrial oxidative damage, mitochondrial fragmentation, mitochondrial metabolism disruption, and mitochondrial apoptosis activation. Furthermore, we verified that LPS modulated mitochondrial apoptosis by promoting Bax upregulation, and this process was regulated by the JNK-Bnip3 pathway. Inhibition of the JNK-Bnip3 pathway prevented LPS-mediated Bax activation, thus attenuating OEG apoptosis. Altogether, our data illustrated that LPS-mediated inflammation injury evoked mitochondrial abnormalities in OEG damage via the JNK-Bnip3-Bax pathway. This finding provides a potential target to protect OEG against chronic inflammation stress.

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Section: Introductionmentioning

confidence: 99%

Lipopolysaccharide induces human olfactory ensheathing glial apoptosis by promoting mitochondrial dysfunction and activating the JNK-Bnip3-Bax pathway

Xiang

et al. 2019

Cell Stress and Chaperones

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“…Our data further demonstrated broad changes in expression of genes encoding proteins involved in epigenetic regulation of transcription, mainly histone deacetylases and BET proteins. The significant role of increased acetylation of histone H3 in regulating transcription of pro-inflammatory genes and, in consequence, in neuronal and microglial neuro-inflammatory response, was demonstrated in the rat hypothalamus and hippocampus after peripheral administration of LPS [63]. However, inhibitors of HDAC were shown to suppress expression of pro-inflammatory mediators in glial cultures exposed to LPS [64].…”

Section: Discussionmentioning

confidence: 99%

Acute Systemic Inflammatory Response Alters Transcription Profile of Genes Related to Immune Response and Ca2+ Homeostasis in Hippocampus; Relevance to Neurodegenerative Disorders

Czapski

Zhao

Lukiw

et al. 2020

IJMS

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Acute systemic inflammatory response (SIR) triggers an alteration in the transcription of brain genes related to neuroinflammation, oxidative stress and cells death. These changes are also characteristic for Alzheimer’s disease (AD) neuropathology. Our aim was to evaluate gene expression patterns in the mouse hippocampus (MH) by using microarray technology 12 and 96 h after SIR evoked by lipopolysaccharide (LPS). The results were compared with microarray analysis of human postmortem hippocampal AD tissues. It was found that 12 h after LPS administration the expression of 231 genes in MH was significantly altered (FC > 2.0); however, after 96 h only the S100a8 gene encoding calgranulin A was activated (FC = 2.9). Gene ontology enrichment analysis demonstrated the alteration of gene expression related mostly to the immune-response including the gene Lcn2 for Lipocalin 2 (FC = 237.8), involved in glia neurotoxicity. The expression of genes coding proteins involved in epigenetic regulation, histone deacetylases (Hdac4,5,8,9,11) and bromo- and extraterminal domain protein Brd3 were downregulated; however, Brd2 was found to be upregulated. Remarkably, the significant increase in expression of Lcn2, S100a8, S100a9 and also Saa3 and Ch25h, was found in AD brains suggesting that early changes of immune-response genes evoked by mild SIR could be crucial in AD pathogenesis.

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“…An increasing number of studies have identified that mitochondrial dysfunction contributes to epigenetic modification (reviewed Minocherhomji et al, 2012). Thus, given the literature showing 2HG as an epigenetic modifier, it is reasonable to predict that S-2HG may cause epigenetic modification of the iNOS promoter, leading to its suppressed activity (Rigillo et al, 2018). Inhibition of 2-oxoglutaratedependent dioxygenases, that demethylate histones (Jumonji C containing proteins) or oxidize 5-methylcytosine in DNA (Ten-eleven translocation (Tet) proteins) could mediate S-2HG's effect.…”

Section: Discussionmentioning

confidence: 99%

2-Hydroxyglutarate Metabolism Is Altered in an in vivo Model of LPS Induced Endotoxemia

et al. 2020

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The metabolic response to endotoxemia closely mimics those seen in sepsis. Here, we show that the urinary excretion of the metabolite 2-hydroxyglutarate (2HG) is dramatically suppressed following lipopolysaccharide (LPS) administration in vivo, and in human septic patients. We further show that enhanced activation of the enzymes responsible for 2-HG degradation, D-and L-2-HGDH, underlie this effect. To determine the role of supplementation with 2HG, we carried out co-administration of LPS and 2HG. This co-administration in mice modulates a number of aspects of physiological responses to LPS, and in particular, protects against LPS-induced hypothermia. Our results identify a novel role for 2HG in endotoxemia pathophysiology, and suggest that this metabolite may be a critical diagnostic and therapeutic target for sepsis.

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LPS-induced histone H3 phospho(Ser10)-acetylation(Lys14) regulates neuronal and microglial neuroinflammatory response

Cited by 39 publications

References 98 publications

Lipopolysaccharide induces human olfactory ensheathing glial apoptosis by promoting mitochondrial dysfunction and activating the JNK-Bnip3-Bax pathway

Lipopolysaccharide induces human olfactory ensheathing glial apoptosis by promoting mitochondrial dysfunction and activating the JNK-Bnip3-Bax pathway

Acute Systemic Inflammatory Response Alters Transcription Profile of Genes Related to Immune Response and Ca2+ Homeostasis in Hippocampus; Relevance to Neurodegenerative Disorders

2-Hydroxyglutarate Metabolism Is Altered in an in vivo Model of LPS Induced Endotoxemia

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