Mitochondrial pyruvate carrier 1 alleviates hypoxic-ischemic brain injury in rats

Liu, Yue; Yuan, Yuan; Yan, Yi; Wang, Ruyue; Wang, Zhaohui; Liu, Xiao; Zhang, Ying; Hua, Jianyu; Wang, Yue; Zhao, Li

doi:10.1016/j.lfs.2023.121686

Cited by 4 publications

(2 citation statements)

References 60 publications

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“…In addition, relevant studies have shown that the PI3K/AKT/mTOR signaling pathway mediates the pathological injury process after cerebral ischemiareperfusion is a target of ischemic brain injury protection. Activate this pathway can alleviate neonatal hypoxic-ischemic brain injury, repair neurological function after stroke, and provide neuroprotection [15,16] . Activation of PI3K/AKT signaling pathway can reduce the expression of in ammatory factors and protect vascular function [17] .…”

Section: Discussionmentioning

confidence: 99%

Hypothermia prevents OGD/R induced injury by activating the PI3K/AKT/mTOR signaling pathway and enhancing autophagy

Shi,

Gao,

Wang

et al. 2024

Preprint

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Objectives To evaluate the role of hypothermia in the injury of PC12 cells which induced by OGD/R. To investigate the mechanism of hypothermia intervention to alleviate OGD/R-induced injury of PC12 cells through phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway and autophagy, and to lay a foundation and provide theoretical basis for clinical application of hypothermia on protect nerve injury in the future. Methods Induce PC12 cells establish an Ischemia reperfusion injury model in vitro by OGD/R. Then, intervene PC12 cells with OGD/R and OGD/R treated with LY294002 inhibitor at 37℃, 32℃, 27℃. Valuate cell viability by CCK-8 assay, detect the phosphorylation levels of PI3K, AKT and mTOR proteins through western blotting, evaluate signaling pathway activation of PI3K/AKT/mTOR, detect protein expression of LC3I/II by immunofluorescence and western blotting, and observe the autophagosomes by fluoroscopic electron microscopy to evaluate autophagy. Detect apoptosis by flow cytometry, and evaluate the cell damage. Results Hypothermia treatment could effectively improve the cell viability of PC12 cells treated with OGD/R, and the cell viability increased with the decrease of temperature (P < 0.05). Hypothermia treatment also promoted the increase of the phosphorylation levels of PI3K, AKT and mTOR proteins in cells (P < 0.05). In addition, flow cytometry was used to detect the apoptosis rate of different treatments, and the results showed that hypothermia could inhibit the apoptosis that induced by OGD/R. In the control group, OGD/R group and LY294002 inhibitor group, autophagy specific protein LC3I/II which labeled with green fluorescently was increased significantly under the culture conditions of 32℃ and 27℃, and the fluorescence signal was enhanced. Meanwhile, the expression level of LC3I/II also increased. Autophagosome was increased under the electron microscopy. Conclusion Hypothermia can inhibit apoptosis by regulating the PI3K/AKT/mTOR axis and the level of autophagy, thus protecting PC12 cell damage that induced by OGD/R.

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Section: Discussionmentioning

confidence: 99%

Hypothermia prevents OGD/R induced injury by activating the PI3K/AKT/mTOR signaling pathway and enhancing autophagy

Shi,

Gao,

Wang

et al. 2024

Preprint

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“…As we previously reported,[ 24 ] total RNA extraction and RT to produce cDNA were performed, and then the mRNA expressions of the interested genes were measured by SYBR Green qPCR SuperMix (4367659, Thermo, USA). The mRNA level of each gene was normalized with YWHAZ.…”

Section: Methodsmentioning

confidence: 99%

Identification of brain endothelial cell-specific genes and pathways in ischemic stroke by integrated bioinformatical analysis

Yan,

Wang,

Liu

et al. 2023

Brain Circulation

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BACKGROUND: Ischemic stroke (IS) is a life-threatening condition with limited treatment options; thus, finding the potential key genes for novel therapeutic targets is urgently needed. This study aimed to explore novel candidate genes and pathways of brain microvessel endothelial cells (ECs) in IS by bioinformatics analysis. MATERIALS AND METHODS: The gene expression profiles of brain tissues or brain ECs in IS mice were downloaded from the online gene expression omnibus (GEO) to obtain the differentially expressed genes (DEGs) by R software. Functional enrichment analyses were used to cluster the functions and signaling pathways of the DEGs, while DEG-associated protein–protein interaction network was performed to identify hub genes. The target microRNAs and competitive endogenous RNA networks of key hub genes were constructed by Cytoscape. RESULTS: Totally 84 DEGs were obtained from 6 brain tissue samples and 4 brain vascular EC samples both from IS mice in the datasets GSE74052 and GSE137482, with significant enrichment in immune responses, such as immune system processes and T-cell activation. Eight hub genes filtered by Cytoscape were validated by two other GEO datasets, wherein key genes of interest were verified by reverse transcription-polymerase chain reaction using an in vitro ischemic model of EC cultures. Our data indicated that AURKA and CENPF might be potential therapeutic target genes for IS, and Malat1/Snhg12/Xist-miR-297b-3p-CENPF, as well as Mir17 hg-miR-34b-3p-CENPF, might be RNA regulatory pathways to control IS progression. CONCLUSIONS: Our work identified two brain EC-specific expressed genes in IS, namely, AURKA and CENPF, as potential gene targets for IS treatment. In addition, we presented miR-297b-3p/miR-34b-3p-CENPF as the potential RNA regulatory axes to prevent pathogenesis of IS.

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The Role of Mitochondrial Pyruvate Carrier in Neurological Disorders

Liu,

Yu,

Jiang

2024

Mol Neurobiol

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Mitochondrial pyruvate carrier 1 alleviates hypoxic-ischemic brain injury in rats

Cited by 4 publications

References 60 publications

Hypothermia prevents OGD/R induced injury by activating the PI3K/AKT/mTOR signaling pathway and enhancing autophagy

Hypothermia prevents OGD/R induced injury by activating the PI3K/AKT/mTOR signaling pathway and enhancing autophagy

Identification of brain endothelial cell-specific genes and pathways in ischemic stroke by integrated bioinformatical analysis

The Role of Mitochondrial Pyruvate Carrier in Neurological Disorders

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