Suppression of lncRNA RMRP ameliorates oxygen-glucose deprivation/re-oxygenation-induced neural cells injury by inhibiting autophagy and PI3K/Akt/mTOR-mediated apoptosis

Zhou, Zheyi; Xu, Hong; Liu, Baozhu; Dun, Linglu; Lu, Changjun; Cai, Yefeng

doi:10.1042/bsr20181367

Cited by 17 publications

(17 citation statements)

References 23 publications

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“…Wang et al suggested that Homer1a relieved neuronal injury induced by traumatic damage by inhibiting PI3K/AKT/mTOR signaling ( Wang et al, 2020 ). PI3K/Akt/mTOR signaling was also involved in oxygen-glucose deprivation/re-oxygenation-induced neuron injury ( Zhou et al, 2019 ). In addition, NF-κB pathway can be activated by Akt protein kinases and involved in various functions, such as immune, inflammation, apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…Mounting evidence indicated that the activation of NF-κB signaling pathway was relevant to nerve injury ( Theus et al, 2017 ; Mettang et al, 2018 ). Indeed, it has also been demonstrated that Akt signaling pathway is involved in neuronal injury ( Zhou et al, 2019 ; Wang et al, 2020 ). Phosphorylation of Akt can activate IKKs, leading to phosphorylation and degradation of IKB, p65 nuclear translocation ( Ya et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

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High Expression of Lysophosphatidic Acid Induces Nerve Injury in LSS Patients via AKT Mediated NF-κB p65 Pathway

Zhai¹,

Liang

2021

Front. Pharmacol.

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Lumbar spinal stenosis (LSS) is a spinal degenerative disease, complicated with nerve injury. Lysophosphatidic acid (LPA), a kind of glycerophospholipid molecule is elevated in the initial stages of neural injury. This research aimed to investigate the patho-mechanism of nerve injury caused by LPA in LSS patients. Twenty-five LSS patients and fifteen idiopathic scoliosis patients (without neurological symptoms) were recruited from Xianyang Central Hospital of Shanxi Province. We measured the concentration of LPA in cerebrospinal fluid samples of all subjects. Different concentrations (0.1, 1, and 10 mol/L) of LPA were used to stimulate Rat Neurons-spinal cord (RN-SC) cells. The effects of LPA on cell injury was detected by MTT and LDH (lactate dehydrogenase) assay. Cell apoptosis was determined by FCM (flow cytometry) and TUNEL staining. The changes in the expression of key proteins involved in Akt mediated NF-κB p65 pathway intervened by LPA were determined by western blot. RN-SC cells were pretreated with JSH-23 (NF-κB inhibitor) before LPA exposure, followed by cell apoptosis measurement. The concentration of LPA in LSS patients was notably higher than that in control patients (p < 0.01). The level of LPA was positively correlated with the severity of LSS. LPA treatment induced RN-SC cells displaying oval or rounded cell body with degenerated protrusion dose dependently. In addition, LPA decreased RN-SC cell viability and promoted cell apoptosis in a dose-dependent manner. LPA initiated Akt phosphorylation, IKB phosphorylation, and NF-κB nuclear translocation in a dose-dependent manner. However, JSH-23 (NF-κB inhibitor) pre-treatment prevented effects of LPA. The high levels of LPA induced nerve injury by reducing the viability of RN-SC cells and promoted cell apoptosis through Akt mediated NF-κB p65 signaling pathway. LPA might be a new therapeutic target for relieving nerve injury in LSS patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

High Expression of Lysophosphatidic Acid Induces Nerve Injury in LSS Patients via AKT Mediated NF-κB p65 Pathway

Zhai¹,

Liang

2021

Front. Pharmacol.

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“…The results indicated that MCAO treatment caused noticeably increased infarcted size in mice (Figure 1 It has been reported that RMRP inhibition improves OGD/Rinduced neuron damage, 11 and miR-613 can inhibit I/R-induced cardiomyocyte apoptosis. 16 In addition, ATG3 also plays a role in I/R injury.…”

Section: Lncrna Rmrp and Atg3 Was Significantly Highly Expressed In Mcao Mouse Brainmentioning

confidence: 92%

“…9 The effect of RMRP on the pathogenesis of brain disease has been verified, and RMRP is tightly associated with I/R injury. 10,11 However, the underlying mechanism of RMRP in cerebral I/R injury remains elusive.…”

Section: Introductionmentioning

confidence: 99%

Knockdown of long non‐coding RNA RMRP protects cerebral ischemia–reperfusion injury via the microRNA‐613/ATG3 axis and the JAK2/STAT3 pathway

Peng

Yang

et al. 2021

The Kaohsiung J of Med Scie

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Cerebral ischemia-reperfusion (I/R) injury can induce the mitophagy of neurons in the ischemic brain. Long non-coding RNAs (lncRNAs) play an important role in the pathogenesis of various injuries, especially in cerebral I/R injury. The purpose of this study is to investigate the molecular mechanism of lncRNA RNA component of mitochondrial RNA processing endoribonuclease (RMRP) in cerebral I/R injury. The middle cerebral artery occlusion (MCAO) mouse model was established. Neurological deficit score, pathological structure, infarcted area, neuron number, cell apoptosis, and coagulation ability of MCAO mice were evaluated. The expressions of RMRP, microRNA (miR)-613, and ATG3 in MCAO mice were detected. The binding relationships among miR-613, RMRP, and ATG3 were predicted and verified. Neuro 2A (N2a) cells were treated with oxygen-glucose deprivation/reperfusion (OGD/R) to simulate I/R injury. Cell viability and apoptosis assays were performed. The effects of miR-613, ATG3, and RMRP on I/R injury were verified by functional rescue experiments. JAK2/STAT3 phosphorylation level was detected. We found significantly upregulated RMRP and ATG3, and downregulated miR-613 expressions in MCAO mice. RMRP could escalate ATG3 mRNA expression through miR-613. RMRP knockdown promoted viability and inhibited apoptosis of OGD/R-treated N2a cells, which could be reversed by miR-613 inhibition or ATG3 overexpression. RMRP overexpression inhibited the activation of JAK2/STAT3 signaling pathway. We demonstrated that lncRNA RMRP competitively bound to miR-613, leading to the increase of ATG3 expression and the inhibition the JAK2/STAT3 pathway, thus promoting cerebral I/R injury in mice.

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“…However, if the stress is prolonged or extensive, homeostasis within the cell is disrupted leading to apoptosis, which is primarily mediated by Ca 2+ overload, or autophagy (Berridge et al, 2000 ; Bernales et al, 2006 ; Ding et al, 2007 ; Høyer-Hansen and Jäättelä, 2007 ). Autophagy, e.g., caused by oxygen and glucose deprivation and reoxygenation, may maintain cellular homeostasis, but its excessive level may lead to autophagic neuronal necrosis and apoptosis (Ahsan et al, 2019 ; Zhou et al, 2019 ). Differences in cytosolic Ca 2+ levels associated with autophagy and apoptosis have been demonstrated in several cell lines.…”

Section: Stim Proteins In the Physiology Of Neurons Autophagy And Nmentioning

confidence: 99%

Target Molecules of STIM Proteins in the Central Nervous System

Serwach

Gruszczynska-Biegala

2020

Front. Mol. Neurosci.

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Stromal interaction molecules (STIMs), including STIM1 and STIM2, are single-pass transmembrane proteins that are located predominantly in the endoplasmic reticulum (ER). They serve as calcium ion (Ca2+) sensors within the ER. In the central nervous system (CNS), they are involved mainly in Orai-mediated store-operated Ca2+ entry (SOCE). The key molecular components of the SOCE pathway are well-characterized, but the molecular mechanisms that underlie the regulation of this pathway need further investigation. Numerous intracellular target proteins that are located in the plasma membrane, ER, cytoskeleton, and cytoplasm have been reported to play essential roles in concert with STIMs, such as conformational changes in STIMs, their translocation, the stabilization of their interactions with Orai, and the activation of other channels. The present review focuses on numerous regulators, such as Homer, SOCE-associated regulatory factor (SARAF), septin, synaptopodin, golli proteins, partner of STIM1 (POST), and transcription factors and proteasome inhibitors that regulate STIM-Orai interactions in the CNS. Further we describe novel roles of STIMs in mediating Ca2+ influx via other than Orai pathways, including TRPC channels, VGCCs, AMPA and NMDA receptors, and group I metabotropic glutamate receptors. This review also summarizes recent findings on additional molecular targets of STIM proteins including SERCA, IP3Rs, end-binding proteins (EB), presenilin, and CaMKII. Dysregulation of the SOCE-associated toolkit, including STIMs, contributes to the development of neurodegenerative disorders (e.g., Alzheimer's disease, Parkinson's disease, and Huntington's disease), traumatic brain injury, epilepsy, and stroke. Emerging evidence points to the role of STIM proteins and several of their molecular effectors and regulators in neuronal and glial physiology and pathology, suggesting their potential application for future therapeutic strategies.

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Suppression of lncRNA RMRP ameliorates oxygen-glucose deprivation/re-oxygenation-induced neural cells injury by inhibiting autophagy and PI3K/Akt/mTOR-mediated apoptosis

Cited by 17 publications

References 23 publications

High Expression of Lysophosphatidic Acid Induces Nerve Injury in LSS Patients via AKT Mediated NF-κB p65 Pathway

High Expression of Lysophosphatidic Acid Induces Nerve Injury in LSS Patients via AKT Mediated NF-κB p65 Pathway

Knockdown of long non‐coding RNA RMRP protects cerebral ischemia–reperfusion injury via the microRNA‐613/ATG3 axis and the JAK2/STAT3 pathway

Target Molecules of STIM Proteins in the Central Nervous System

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