&lt;p&gt;Sevoflurane post-conditioning alleviates neonatal rat hypoxic-ischemic cerebral injury via Ezh2-regulated autophagy&lt;/p&gt;

Xue, Hang; Xu, Ying; Wang, Shuo; Wu, Ziyi; Li, Xing-Yue; Zhang, Yahan; Niu, Jiayuan; Gao, Qiushi; Zhao, Ping

doi:10.2147/dddt.s197325

Cited by 39 publications

(33 citation statements)

References 49 publications

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“…Excessive autophagy caused by HIBI may cause neuronal death [4]. Our previous studies revealed that the volatile anesthetic sevo urane could exert neuroprotective effects against HIBI via autophagy inhibition [14,15]. Yet, the underlying mechanisms remain unclear.…”

Section: Discussionmentioning

confidence: 99%

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Sevoflurane post-conditioning alleviated hypoxic-ischemic brain injury in neonatal rats by inhibiting endoplasmic reticulum stress-mediated autophagy via IRE1 signalings

Niu

Xue

et al. 2021

Preprint

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Post-conditioning with sevoflurane, a volatile anesthetic, has been proved to be neuroprotective against hypoxic-ischemic brain injury (HIBI). Our previous research showed that autophagy is over-activated in a neonatal HIBI rat model, and inhibition of autophagy confers neuroprotection. There is increasing recognition that autophagy can be stimulated by activating endoplasmic reticulum (ER) stress. Herein, we purposed to explore: i) the association of ER stress with autophagy in the setting of neonatal HIBI; and ii) the possible roles of ER stress-triggered autophagy, as well as IRE1 signaling in the neuroprotection of sevoflurane post-conditioning against neonatal HIBI. Seven-day-old rats underwent ligation of the left common artery, and a subsequent 2 hour hypoxia (8% O2 / 92% N2). The association of ER stress with autophagy was examined by ER stress inducer (tunicamycin), 4-PBA (ER stress inhibitor), or 3-MA (autophagy inhibitor). Rats in the sevoflurane post-conditioning groups were treated with 2.4% sevoflurane for 30 minutes after HIBI stimulation. The roles of ER stress-mediated autophagy, as well as the IRE1-JNK-beclin1 signaling cascade in the neuroprotection afforded by sevoflurane were explored by ER stress inducer (tunicamycin) and the IRE1 inhibitor (STF-083010). HIBI over‑activated ER stress and autophagy in neonatal rats. HIBI-induced autophagy was significantly aggravated by tunicamycin but blocked by 4-PBA; however, HIBI-induced ER stress was not affected by 3-MA. Sevoflurane post-conditioning significantly alleviated ER stress, autophagy, cell apoptosis, and cognitive impairments, which were remarkably abolished by tunicamycin. Also, tunicamycin blocked sevoflurane-induced downregulation of IRE1-JNK-beclin1 signaling pathway. Whereas, IRE1 inhibitor could reverse the effects of tunicamycin. ER stress contributes to autophagy induced by HIBI. Furthermore, sevoflurane post-conditioning significantly protects against HIBI in neonatal rats by inhibiting ER stress-mediated autophagy via IRE1-JNK-beclin1 signaling cascade.

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Section: Discussionmentioning

confidence: 99%

“…Our previous researches indicated that sevo urane-conferred neuroprotection against HIBI is linked to repressed excessive autophagy [14,15]. TM was applied in order to elucidate whether inhibition of autophagy by sevo urane was mediated through suppressing ER stress.…”

Section: Sevo Urane Post-conditioning Alleviated Er Stress-mediated Amentioning

confidence: 99%

Sevoflurane post-conditioning alleviated hypoxic-ischemic brain injury in neonatal rats by inhibiting endoplasmic reticulum stress-mediated autophagy via IRE1 signalings

Niu

Xue

et al. 2021

Preprint

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“…In this regard, volatile anesthetics, i.e., sevoflurane and isoflurane, have shown to be neuroprotective against HI brain damage in neonatal rats (152,153) (Table 2). Diverse studies have shown sevoflurane inhibits excessive hippocampal autophagy increasing the expression of EZH2, H3K27me3, and decreased expression of PTEN induced by HI, improving the behavioral outcome (154).…”

Section: Histone Methylationmentioning

confidence: 99%

Clinical Implications of Epigenetic Dysregulation in Perinatal Hypoxic-Ischemic Brain Damage

et al. 2020

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Placental and fetal hypoxia caused by perinatal hypoxic-ischemic events are major causes of stillbirth, neonatal morbidity, and long-term neurological sequelae among surviving neonates. Brain hypoxia and associated pathological processes such as excitotoxicity, apoptosis, necrosis, and inflammation, are associated with lasting disruptions in epigenetic control of gene expression contributing to neurological dysfunction. Recent studies have pointed to DNA (de)methylation, histone modifications, and non-coding RNAs as crucial components of hypoxic-ischemic encephalopathy (HIE). The understanding of epigenetic dysregulation in HIE is essential in the development of new clinical interventions for perinatal HIE. Here, we summarize our current understanding of epigenetic mechanisms underlying the molecular pathology of HI brain damage and its clinical implications in terms of new diagnostic, prognostic, and therapeutic tools.

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“…The role of EZH2 in cancer progression and malignancy has been extensively studied in the last decade ( Liu et al, 2018 ; Emran et al, 2019 ). Moreover, growing evidences demonstrate that downregulation of EZH2 was essential for inducing autophagy and apoptosis in many types of cancer cells ( Xue et al, 2019 ; Liu et al, 2020 ). However, the exact role EZH2 plays in trophoblastic autophagy has not been fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

Amnion-Derived Mesenchymal Stem Cell Exosomes-Mediated Autophagy Promotes the Survival of Trophoblasts Under Hypoxia Through mTOR Pathway by the Downregulation of EZH2

Chu

Chen

Peng

et al. 2020

Front. Cell Dev. Biol.

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Human amnion-derived mesenchymal stem cells (AD-MSCs) have been reported as a promising effective treatment to repair tissue. Trophoblast dysfunction during pregnancy is significantly involved in the pathogenesis of preeclampsia (PE). To understand how AD-MSCs regulated trophoblast function, we treated trophoblasts with AD-MSC-derived exosomes under hypoxic conditions. The treatment markedly enhanced the trophoblast proliferation and autophagy. Furthermore, significant decrease of EZH2 levels and inactivation of mTOR signaling were observed in AD-MSC exosomes-treated trophoblasts. Consistent with these findings, overexpression of EZH2 activated the mTOR signaling in trophoblasts, and reduced the autophagy and survival of trophoblasts, even in the presence of AD-MSC-derived exosomes. In addition, EZH2 inhibition exhibited the same trophoblast autophagy-promoting effect as induced by AD-MSC-derived exosomes, also accompanied by the inactivation of mTOR signaling. Importantly, when EZH2 was overexpressed in trophoblasts treated with PQR620, a specific mTOR signaling inhibitor, the autophagy and proliferation in trophoblasts were decreased. Studies on human placental explants also confirmed our findings by showing that the expression levels of EZH2 and mTOR were decreased while the autophagy-associated protein level was increased by AD-MSC-derived exosome treatment. In summary, our results suggest that EZH2-dependent mTOR signaling inactivation mediated by AD-MSC-derived exosomes is a prerequisite for autophagy augmentation in hypoxic trophoblasts.

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<p>Sevoflurane post-conditioning alleviates neonatal rat hypoxic-ischemic cerebral injury via Ezh2-regulated autophagy</p>

Cited by 39 publications

References 49 publications

Sevoflurane post-conditioning alleviated hypoxic-ischemic brain injury in neonatal rats by inhibiting endoplasmic reticulum stress-mediated autophagy via IRE1 signalings

Sevoflurane post-conditioning alleviated hypoxic-ischemic brain injury in neonatal rats by inhibiting endoplasmic reticulum stress-mediated autophagy via IRE1 signalings

Clinical Implications of Epigenetic Dysregulation in Perinatal Hypoxic-Ischemic Brain Damage

Amnion-Derived Mesenchymal Stem Cell Exosomes-Mediated Autophagy Promotes the Survival of Trophoblasts Under Hypoxia Through mTOR Pathway by the Downregulation of EZH2

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