Sirtuin 6 protects the brain from cerebral ischemia/reperfusion injury through NRF2 activation

Paraoxonase 2 (PON2) is a powerful antioxidant that mediates cell survival under oxidative stress; however, its protection neurons against cerebral ischemia-reperfusion injury-induced oxidative stress remains unclear. This study aimed to determine the precise regulating role of PON2 in neuronal survival under oxidative stress. An in vitro model of cerebral ischemia-reperfusion injury was used to assess the effect of PON2 on oxidative stress induced by oxygen–glucose deprivation/reoxygenation (OGD/R). Results showed that PON2 expression in neurons was decreased due to OGD/R exposure. A series of functional experiments revealed that upregulated PON2 improved OGD/R-impaired viability and attenuated OGD/R-induced increases in apoptosis and reactive oxygen species in neurons. Decreased PON2 expression enhanced neuronal sensitivity to OGD/R-induced injury. Overexpressed PON2 markedly enhanced the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) in the nucleus and increased the levels of Nrf2-mediated transcriptional activity. Furthermore, PON2 enhanced the Nrf2 activation by modulating glycogen synthase kinase-3β (GSK-3β). Inhibition of GSK-3β substantially abrogated the PON2 knockdown-mediated suppression of Nrf2 activity. Notably, Nrf2 inhibition partially reversed the neuroprotective effects of PON2 overexpression in OGD/R-exposed neurons. These findings indicate that PON2 alleviates OGD/R-induced apoptosis and oxidative stress in neurons by potentiating Nrf2 activation via GSK-3β modulation. This study highlights the potential neuroprotective function of PON2 against cerebral ischemia-reperfusion injury.

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LncRNA CEBPA-AS1 Alleviates Cerebral Ischemia-Reperfusion Injury by Sponging miR-340-5p to Regulate APPL1/LKB1/AMPK Pathway

10.21203/rs.3.rs-32933/v1 ◽

2020 ◽

Author(s):

Xiankun Tu ◽

Huabin Zhang ◽

Bin Huang ◽

Xiyao Wu ◽

Songsheng Shi

Keyword(s):

Cerebral Ischemia ◽

Cell Survival ◽

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Cell Damage ◽

Ischemia Reperfusion ◽

Ampk Pathway ◽

Cerebral Ischemia Reperfusion ◽

Cerebral Ischemia Reperfusion Injury ◽

The Brain

Abstract BACKGROUND: The aim of this study was to research the mechanism of lncRNA CEBPA-AS1 in cerebral ischemia-reperfusion injury (CIRI). METHODS: Middle cerebral artery occlusion (MCAO), MCAO/IR and OGD/R models were constructed. RNA immunoprecipitation (RIP) detected the binding of miR-340-5p to CEBPA-AS1. CEBPA-AS1 and miR-340-5p was knockdown or up-regulated. RT-PCR and western blot was processed to detect the expression of related genes and proteins. Brain tissue water content in each group was determined. Nissl staining in hippocampus of the brain and NeuN staining (green) assay was used to observe nerve damage and detect nerve cell survival, respectively. Cell viability was detected by MTT assay. Nerve cell survival was observed by immunofluorescence cytochemistry assay. LDH and MDA content were detected by kit. TUNEL was used to detect apoptosis. Luciferase reporter system was processed for verifying the binding sites. After overexpressing CEBPA-AS1 in PC-12 cells, RNA pulldown assay was performed. TTC assay was used to observe the general morphology of the brain. RESULTS: Overexpression of CEBPA-AS1 attenuated MCAO/IR-induced nerve damage. Increased CEBPA-AS1 expression reduced neuronal apoptosis in MCAO/IR model. Knockdown of CEBPA-AS1 aggravated cell damage OGD/R cell model. CEBPA-AS1 increased APPL1 expression via negatively regulating miR-340-5p, and affected APPL1/LKB1/AMPK pathway. CEBPA-AS1 attenuated OGD/R-induced cell damage by reducing miR-340-5p levels. CONCLUSIONS: LncRNA CEBPA-AS1 could alleviate cerebral ischemia-reperfusion injury by sponging miR-340-5p to regulate APPL1/LKB1/AMPK pathway.

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Interleukin 15 blockade protects the brain from cerebral ischemia-reperfusion injury

Brain Behavior and Immunity ◽

10.1016/j.bbi.2018.06.021 ◽

2018 ◽

Vol 73 ◽

pp. 562-570 ◽

Cited By ~ 16

Author(s):

Gilbert Aaron Lee ◽

Teng-Nan Lin ◽

Cheng-Yu Chen ◽

Shin-Yi Mau ◽

Wan-Zhen Huang ◽

...

Keyword(s):

Cerebral Ischemia ◽

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Cerebral Ischemia Reperfusion ◽

Cerebral Ischemia Reperfusion Injury ◽

Interleukin 15 ◽

The Brain

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Effects of Thymoquinone on Small-Molecule Metabolites in a Rat Model of Cerebral Ischemia Reperfusion Injury Assessed using MALDI-MSI

Metabolites ◽

10.3390/metabo10010027 ◽

2020 ◽

Vol 10 (1) ◽

pp. 27 ◽

Cited By ~ 2

Author(s):

Fang Tian ◽

Runzhe Liu ◽

Chaoxin Fan ◽

Yi Sun ◽

Xi Huang ◽

...

Keyword(s):

Cerebral Ischemia ◽

Reperfusion Injury ◽

Small Molecule ◽

Rat Model ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Ionization Mass ◽

Cerebral Ischemia Reperfusion ◽

Cerebral Ischemia Reperfusion Injury ◽

The Brain

Thymoquinone is one of the main components present in Nigella sativa seeds and is known to have various biological functions in inflammation, oxidative stress, tumors, aging, and in lowering blood glucose levels. Few studies have focused on its neuroprotective effects and its regulation of small-molecule metabolites during cerebral ischemia reperfusion injury. In this study, transient middle cerebral occlusion (tMCAO) was used to establish the rat model of cerebral ischemia reperfusion injury. We investigated the effects of thymoquinone using matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) in a model of ischemia reperfusion injury to explore the changes in small-molecule metabolites in the brain. We found that that thymoquinone significantly improved neurobehavioral scores, reduced the cerebral infarct area, alleviated brain edema, and increased the number of normal neurons following injury. MALDI-MSI revealed that thymoquinone reduced abnormal accumulations of glucose, citric acid, succinate and potassium ions. Thymoquinone also increased the amount of energy-related molecules such as ADP, AMP, GMP, and creatine, antioxidants such as glutathione, ascorbic acid, and taurine, and other metabolism-related molecules such as glutamate, glutamine, aspartate, N-acetyl-L-aspartate, and sodium ions in damaged areas of the brain following cerebral ischemia reperfusion injury. In summary, based on the neuroprotective effect of thymoquinone on cerebral ischemia reperfusion injury, this study revealed the regulation of thymoquinone on energy metabolism and small-molecule substance metabolism.

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