Dexmedetomidine alleviates hepatic ischaemia‐reperfusion injury via the PI3K/AKT/Nrf2‐NLRP3 pathway

Yan, Wei; Qiu, Gaolin; Zhang, Hai-nie; Zhu, Leilei; Gao, Cheng; Wang, Yiqiao; Li, Yuanhai; Wu, Weiwei

doi:10.1111/jcmm.16871

Cited by 36 publications

(27 citation statements)

References 59 publications

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“…It has been shown that the PI3K/AKT/GSK3β signaling pathway plays a pivotal role in alleviating early brain injury in stroke, including SAH and cerebral ischemia (Chen S. et al, 2014 ; Ma et al, 2016 ). A previous study has reported that Dex was able to alleviate hepatic ischemia–reperfusion injury via the PI3K/AKT/Nrf2-NLRP3 pathway (Wu et al, 2021 ). In this study, we also observed that Dex activated the PI3K /AKT/GSK3β pathway at 24 h after SAH.…”

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine Inhibits Gasdermin D-Induced Pyroptosis via the PI3K/AKT/GSK3β Pathway to Attenuate Neuroinflammation in Early Brain Injury After Subarachnoid Hemorrhage in Rats

Wei

Jin

et al. 2022

Front. Cell. Neurosci.

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Subarachnoid hemorrhage (SAH) is one kind of life-threatening stroke, which leads to severe brain damage. Pyroptosis plays a critical role in early brain injury (EBI) after SAH. Previous reports suggest that SAH-induced brain edema, cell apoptosis, and neuronal injury could be suppressed by dexmedetomidine (Dex). In this study, we used a rat model of SAH to investigate the effect of Dex on pyroptosis in EBI after SAH and to determine the mechanisms involved. Pyroptosis was found in microglia in EBI after SAH. Dex significantly alleviated microglia pyroptosis via reducing pyroptosis executioner GSDMD and inhibited the release of proinflammatory cytokines induced by SAH. Furthermore, the reduction of GSDMD by Dex was abolished by the PI3K inhibitor LY294002. In conclusion, our data demonstrated that Dex reduces microglia pyroptosis in EBI after SAH via the activation of the PI3K/AKT/GSK3β pathway.

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Section: Discussionmentioning

confidence: 99%

Dexmedetomidine Inhibits Gasdermin D-Induced Pyroptosis via the PI3K/AKT/GSK3β Pathway to Attenuate Neuroinflammation in Early Brain Injury After Subarachnoid Hemorrhage in Rats

Wei

Jin

et al. 2022

Front. Cell. Neurosci.

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“…Dexmedetomidine (DEX) is a highly selective α2-adrenergic agonist with analgesic, anti-stress, and anti-inflammatory effects and is commonly used as a sedative and anesthetic in clinical practice [ 5 ]. The protective effects of DEX in H/R-mediated organ injuries have been extensively studied, such as in brain [ 6 ], liver [ 7 ], renal [ 8 ]. Additionally, DEX exerts its role in cardiomyocyte through different mechanisms [ 9–12 ].…”

Section: Introductionmentioning

confidence: 99%

Dexmedetomidine prevents cardiomyocytes from hypoxia/reoxygenation injury via modulating tetmethylcytosine dioxygenase 1-mediated DNA demethylation of Sirtuin1

et al. 2022

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Myocardial hypoxia/reoxygenation (H/R) injury is a common pathological change in patients with acute myocardial infarction undergoing reperfusion therapy. Dexmedetomidine (DEX) has been found to substantially improve ischemia-mediated cell damage. Here, we focus on probing the role and mechanism of DEX in ameliorating myocardial H/R injury. Oxygen–glucose deprivation and reoxygenation (OGD/R) were applied to construct the H/R injury model in human myocardial cell lines. After different concentrations of DEX’s treatment, cell counting kit-8 (CCK-8) assay and BrdU assay were employed to test cell viability. The profiles of apoptosis-related proteins Bcl2, Bax, Bad and Caspase3, 8, 9 were determined by Western blot (WB). The expression of inflammatory factors interleukin 1β (IL-1β) and tumor necrosis factor-α (TNF-α) was checked by reverse transcription-polymerase chain reaction (RT-PCR). By conducting WB, we examined the expression of NF-κB, Sirt1, Tet methylcytosine dioxygenase 1 (TET1) and DNA methylation-related proteins (DNA methyltransferase 1, DNMT1; DNA methyltransferase 3 alpha, DNMT3A; and DNA methyltransferase 3 beta, DNMT3B). Our data showed that OGD/R stimulation distinctly hampered the viability and elevated apoptosis and inflammatory factor expression in cardiomyocytes. DEX treatment notably impeded myocardial apoptosis and inflammation and enhanced cardiomyocyte viability. OGD/R enhanced total DNA methylation levels in cardiomyocytes, while DEX curbed DNA methylation. In terms of mechanism, inhibiting TET1 or Sirtuin1 (Sirt1) curbed the DEX-mediated myocardial protection. TET1 strengthened demethylation of the Sirt1 promoter and up-regulated Sirt1. DEX up-regulates Sirt1 by accelerating TET1 and mediating demethylation of the Sirt1 promoter and improves H/R-mediated myocardial injury.

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“…AKT is a serine/threonine kinase and a downstream signal molecule of PI3K, activated by it ( Li et al, 2017 ). Several studies have reported that the PI3K/Akt pathway is essential for regulating Nrf2/Ho-1 pathway activation and is thus involved in protection against oxidative stress and apoptosis in multiple cell types ( Di Tu et al, 2020 ; Feng et al, 2021 ; Wu et al, 2021 ). Under oxidative stress, the PI3K/Akt signaling pathway leads to Nrf2-dependent transcription and overexpression of HO-1 protein ( He et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Theaflavin Attenuates TBHP-Induced Endothelial Cells Oxidative Stress by Activating PI3K/AKT/Nrf2 and Accelerates Wound Healing in Rats

Chen

et al. 2022

Front. Bioeng. Biotechnol.

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The treatment of wounds remains a clinical challenge because of poor angiogenesis under the wound bed, and increasingly, the patients’ need for functional and aesthetically pleasing scars. Previous reports have shown that Theaflavin can induce angiogenesis and terminate the progression of ischemic cardiovascular disease, but limited therapy is available for the management of cutaneous wounds. In this study, our in vitro work discovered that human umbilical vein endothelial cells (HUVECs) exposed to Theaflavin can alleviate apoptosis and cell dysfunction induced by tert-butyl hydroperoxide (TBHP). The cellular activity of HUVECs were assessed by cell tube formation, migration and adhesion. Mechanistically, Theaflavin protected HUVECs from TBHP-stimulated cell apoptosis through the activation of the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/nuclear factor (erythroid-derived 2)-like 2 (Nrf2) axis, so Nrf2 silencing can partly eliminate the cytoprotective effect of Theaflavin treatment. In in vivo experiments, administering Theaflavin orally can enhance vascularization in regenerated tissues and accelerate wound healing. In summary, our data served as a novel evidence for the wound healing treatment with Theaflavin, and certified the potential mechanism of Theaflavin, which can be used as a potential agent for cutaneous wound therapy.

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Dexmedetomidine alleviates hepatic ischaemia‐reperfusion injury via the PI3K/AKT/Nrf2‐NLRP3 pathway

Cited by 36 publications

References 59 publications

Dexmedetomidine Inhibits Gasdermin D-Induced Pyroptosis via the PI3K/AKT/GSK3β Pathway to Attenuate Neuroinflammation in Early Brain Injury After Subarachnoid Hemorrhage in Rats

Dexmedetomidine Inhibits Gasdermin D-Induced Pyroptosis via the PI3K/AKT/GSK3β Pathway to Attenuate Neuroinflammation in Early Brain Injury After Subarachnoid Hemorrhage in Rats

Dexmedetomidine prevents cardiomyocytes from hypoxia/reoxygenation injury via modulating tetmethylcytosine dioxygenase 1-mediated DNA demethylation of Sirtuin1

Theaflavin Attenuates TBHP-Induced Endothelial Cells Oxidative Stress by Activating PI3K/AKT/Nrf2 and Accelerates Wound Healing in Rats

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