miR-9-5p attenuates ischemic stroke through targeting ERMP1-mediated endoplasmic reticulum stress

Chi, Lumei; Jiao, Dan; Guo, Nan; Yuan, Honghua; Shen, Jing; Gao, Yu

doi:10.1016/j.acthis.2019.08.005

Cited by 32 publications

(23 citation statements)

References 29 publications

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“…Herein, both ER stress along with autophagy are activated in the pathological process of neonatal HIBI, as evidenced by increased GRP78 and LC3BII expression, as well as decreased p62 expression. Our results supported results from previous studies that ER stress along with autophagy are involved in ischemic stroke [19,20]. Of note, to elucidate the association of ER stress with autophagy in the setting of neonatal HIBI, the rats were inocualted with TM (ER stress inducer), 4-PBA (ER stress inhibitor), or 3-MA (autophagy inhibitor).…”

Section: Discussionsupporting

confidence: 90%

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: Discussionsupporting

confidence: 90%

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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“…Using a rat MCAO model, it was shown that MCAO increased expression of Endoplasmic Reticulum Metallopeptidase 1 (ERMP‐1), which is a target of miR‐9. Exogenous overexpression of miR‐9 in OGD neurons decreased ERMP‐1 and rescued OGD‐associated loss of cell viability 28 . It is, however, surprising that this study did not find miR‐9 levels increasing following MCAO, 28 bringing into question the broad applicability of the findings.…”

Section: Discussionmentioning

confidence: 69%

Inhibition of microRNA‐9‐5p and microRNA‐128‐3p can inhibit ischemic stroke‐related cell death in vitro and in vivo

et al. 2020

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Ischemic stroke is the major form of stroke and is accentuated by multiple comorbidities. It has been previously shown that different microRNAs (miRNAs) regulate separate aspects of ischemic stroke. Differential miRNA expression analysis in cerebrospinal fluid of stroke patients had revealed upregulation of miR-124-3p, miR-9-3p, miR-9-5p, and miR-128-3p. However, whether the overexpression is correlative or causative was not known. Here, using an in vitro oxygen-glucose deprivation/reoxygenation (OGD/R) neuronal cell model, we saw OGD/R-induced injury was associated with significant upregulation of the aforementioned four miRNAs. Target gene prediction

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“…Accumulating evidence has shown that ER stress is implicated in the physiopathology of several neurological disorders, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (Cabral-Miranda and Hetz, 2018). ER stress can be triggered by multiple stimuli and pathological conditions, such as hypoxia, ischemia, oxidative injury, and inflammation, which leads to accumulation of misfolded and unfolded proteins (Chi et al, 2019). ER stress activates a group of signal transduction pathways called the UPR to restore ER homeostasis, promoting cell survival and adaptation.…”

Section: Discussionmentioning

confidence: 99%

Sodium 4-Phenylbutyrate Protects Hypoxic-Ischemic Brain Injury via Attenuating Endoplasmic Reticulum Stress in Neonatal Rats

Niu

Xue

et al. 2021

Front. Behav. Neurosci.

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Neonatal hypoxic-ischemic (HI) brain injury is associated with long-term neurological disorders, and protective strategies are presently scarce. Sodium 4-phenylbutyrate (4-PBA) reportedly acts as a chemical chaperone that alleviates endoplasmic reticulum (ER) stress, which plays a critical role in neurological diseases. The present study aimed to evaluate the neuroprotective effects of 4-PBA on HI-induced neonatal brain injury in a rat model, and to characterize possible underlying mechanisms. The HI brain injury model was established by ligating the left common carotid artery in 7-day-old rats, followed by exposure to 8% oxygen for 2 h. The 4-PBA or vehicle was administered by an intracerebroventricular injection 30 min before HI. The protein expression levels of ER stress markers (GRP78, ATF6, and CHOP) were detected by western blotting at 24 h after HI insult. The activation of cAMP-response element-binding protein (CREB) was evaluated by western blotting and immunofluorescence. TUNEL and Nissl staining were performed to detect the histomorphological changes in the hippocampal neurons at 24 h and 7 days, respectively, after HI injury. From days 29 to 34 after brain HI, rats underwent Morris water maze tests to assess cognitive functioning. The results showed that pretreatment with 4-PBA decreased HI-induced excessive ER stress and neuronal injury. Moreover, CREB activation might be involved in the beneficial effects of 4-PBA on HI-induced learning and memory deficits in rats. In conclusion, the present study suggested a potential therapeutic approach of ER stress inhibition in the treatment of neonatal HI brain injury.

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miR-9-5p attenuates ischemic stroke through targeting ERMP1-mediated endoplasmic reticulum stress

Cited by 32 publications

References 29 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

Inhibition of microRNA‐9‐5p and microRNA‐128‐3p can inhibit ischemic stroke‐related cell death in vitro and in vivo

Sodium 4-Phenylbutyrate Protects Hypoxic-Ischemic Brain Injury via Attenuating Endoplasmic Reticulum Stress in Neonatal Rats

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