The mechanism of sevoflurane post-treatment alleviating hypoxic-ischemic encephalopathy by affecting histone methyltransferase G9a in rats

Shan, Weifeng; Wu, Yanzhi; Han, Xin; Chen, Qin; Wu, Jimin

doi:10.1080/21655979.2021.1995105

Cited by 3 publications

(1 citation statement)

References 44 publications

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“…In addition, Takashio and Tschorn et al found that plasma BDNF expression was reduced in patients with HF and associated with HF severity, suggesting that it might be a clinically valuable biomarker of HF [ 27 , 28 ]. After G9a overexpression in vitro and in vivo, the enrichment levels of H3K9me2 in the promoter region of BDNF were augmented, whereas the levels of BDNF were decreased, along with damaged neurons and impaired learning and memory abilities of rats with hypoxic-ischemic encephalopathy [ 29 ]. There findings were largely in line with our observation where enrichment of BDNF promoters by G9a and H3K9me2 was significantly reduced after silencing of G9a in H9C2 cells.…”

Section: Discussionmentioning

confidence: 99%

H3K9me2 regulation of BDNF expression via G9a partakes in the progression of heart failure

Yan

Chen

Cui

2022

BMC Cardiovasc Disord

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Background Heart disease is a major cause of mortality in developed countries. The associated pathology is mainly characterized by the loss of cardiomyocytes that contributes to heart failure (HF). This study aims to investigate the mechanism of euchromatic histone lysine methyltransferase 2 (EHMT2, also term G9a) in HF in rats. Methods Differentially expressed mRNAs in HF were screened using GEO database. Sera from subjects with or without HF were collected, and PCR was performed to detect the G9a expression. G9a was downregulated in cardiomyocytes exposed to oxygen–glucose deprivation (OGD), followed by CCK8, flow cytometry, colorimetric method, and western blot assays. Established HF rats were delivered with lentiviral vectors carrying sh-G9a, and TTC staining, HE staining, TUNEL, ELISA, and western blot were performed. The regulation of G9a on the downstream target BDNF was investigated by RT-qPCR, Western blot, and ChIP-qPCR. Finally, rescue experiments were carried out to substantiate the effect of G9a on cardiomyocyte apoptosis and injury via the BDNF/TrkB axis. Results G9a was overexpressed, whereas BDNF was downregulated in HF. Knockdown of G9a inhibited apoptosis and injury in OGD-treated cardiomyocytes and attenuated the extent of HF and myocardial injury in rats. Silencing of G9a promoted BDNF transcription by repressing H3K9me2 modification of the BDNF promoter. Further depletion of BDNF partially reversed the effect of sh-G9a in alleviating cardiomyocyte apoptosis and injury by inhibiting the TrkB signaling pathway. Conclusion G9a inhibits BDNF expression through H3K9me2 modification, thereby impairing the TrkB signaling pathway and exacerbating the development of HF.

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Section: Discussionmentioning

confidence: 99%

H3K9me2 regulation of BDNF expression via G9a partakes in the progression of heart failure

Yan

Chen

Cui

2022

BMC Cardiovasc Disord

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Histone modifications in hypoxic ischemic encephalopathy: Implications for therapeutic interventions

Ji,

Tian,

Zhang

et al. 2024

Life Sciences

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EHMT2 affects microglia polarization and aggravates neuronal damage and inflammatory response via regulating HMOX1

Yang

Chen

Gao

2023

Translational Neuroscience

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Objective This research was designed to ascertain the function of euchromatic histone lysine methyltransferase 2 (EHMT2) in ischemic stroke-induced neuronal damage and inflammatory response and its regulatory mechanism. Methods Mouse microglia (BV-2 cells) were induced by oxygen glucose deprivation/reoxygenation (OGD/R) to establish a cellular model, and then co-cultured with HT22 hippocampal neurons. After that, HT22 cell viability and apoptosis were evaluated, followed by the measurement of apoptosis-related factors (B-cell lymphoma-2, Bcl-2 associated X, and cleaved-Caspase 3). Meanwhile, the expression of inducible nitric oxide synthase (M1 microglia polarization marker) and arginase 1 (M2 microglia polarization marker) in BV-2 cells was detected, as well as the levels of inflammatory factors (tumor necrosis factor-α, interleukin [IL]-6, IL-10, IL-1β, and IL-4). Additionally, the expression of EHMT2 and heme oxygenase 1 (HMOX1) in BV-2 cells was assessed by quantitative reverse transcription polymerase chain reaction and western blot, and the binding between EHMT2 and HMOX1 was predicted and verified. Results OGD/R treatment led to decreased cell viability and increased cell apoptosis in HT22 cells, and aggravated inflammatory response in BV-2 cells. In OGD/R-induced BV-2 cells, EHMT2 and HMOX1 were increasingly expressed, and knockdown of EHMT2 or HMOX1 in BV-2 cells could inhibit neuronal damage and inflammatory response. Moreover, EHMT2 promoted HMOX1 transcription level by histone methylation. Conclusion Collected evidence showed that down-regulation of EHMT2 relieved neuronal damage and inflammatory response by inhibiting HMOX1 expression.

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The mechanism of sevoflurane post-treatment alleviating hypoxic-ischemic encephalopathy by affecting histone methyltransferase G9a in rats

Cited by 3 publications

References 44 publications

H3K9me2 regulation of BDNF expression via G9a partakes in the progression of heart failure

H3K9me2 regulation of BDNF expression via G9a partakes in the progression of heart failure

Histone modifications in hypoxic ischemic encephalopathy: Implications for therapeutic interventions

EHMT2 affects microglia polarization and aggravates neuronal damage and inflammatory response via regulating HMOX1

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