Electrical stimulation inhibits Val-boroPro-induced pyroptosis in THP-1 macrophages via sirtuin3 activation to promote autophagy and inhibit ROS generation

Liu, Cong; Gao, Ziyu; Zheng, Yinghong; Ye, Ting; Wang, Zitong; Wang, Pengyu; Li, Manman; Dong, Bowen; Yang, Wei; Li, Quanfeng; Qiao, Shupei; Cao, Wang Fang; Shen, Yanqing; Li, Hong; Tian, Weiming; Yang, Liming

doi:10.18632/aging.103038

Cited by 39 publications

(35 citation statements)

References 61 publications

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“…Furthermore, SIRT3 was shown to counteract pyroptosis by promoting autophagy and inhibiting the generation of ROS [ 92 ]. In this study, treatment with Dex suppressed activation of the NLRP3 inflammasome evidenced by the low expression levels of NLRP3, cleaved-caspase-1, ASC, and GSDMD consistent with the NLRP3 immunohistochemical staining results.…”

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine Ameliorates Hippocampus Injury and Cognitive Dysfunction Induced by Hepatic Ischemia/Reperfusion by Activating SIRT3-Mediated Mitophagy and Inhibiting Activation of the NLRP3 Inflammasome in Young Rats

Lyu

Jia

et al. 2020

Oxidative Medicine and Cellular Longevity

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Hepatic ischemia-reperfusion (HIR) has been proven to trigger oxidative stress and pyroptosis in the hippocampus. Sirtuin 3 (SIRT3) is an essential mitochondrial protein deacetylase regulating oxidative stress and mitophagy. Dexmedetomidine (Dex) has been demonstrated to confer neuroprotection in different brain injury models. However, whether the protective effects of Dex following HIR are orchestrated by activation of SIRT3-mediated mitophagy and inhibition of NOD-like receptor protein 3 (NLRP3) inflammasome activation remains unknown. Herein, two-week-old rats were treated with Dex or a selective SIRT3 inhibitor (3-TYP)/autophagy inhibitor (3-MA) and then subjected to HIR. The results revealed that Dex treatment effectively attenuated neuroinflammation and cognitive deficits via upregulating SIRT3 expression and activity. Furthermore, Dex treatment inhibited the activation of NLRP3 inflammasome, while 3-TYP and 3-MA eliminated the protective effects of Dex, suggesting that SIRT3-mediated mitophagy executes the protective effects of Dex. Moreover, 3-TYP treatment downregulated the expression level of SIRT3 downstream proteins: forkhead-box-protein 3α (FOXO3α), superoxide dismutase 2 (SOD2), peroxiredoxin 3 (PRDX3), and cyclophilin D (CYP-D), which were barely influenced by 3-MA treatment. Notably, both 3-TYP and 3-MA were able to offset the antioxidative and antiapoptosis effects of Dex, indicating that SIRT3-mediated mitophagy may be the last step and the major pathway executing the neuroprotective effects of Dex. In conclusion, Dex inhibits HIR-induced NLRP3 inflammasome activation mainly by triggering SIRT3-mediated mitophagy.

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Section: Discussionmentioning

confidence: 99%

Dexmedetomidine Ameliorates Hippocampus Injury and Cognitive Dysfunction Induced by Hepatic Ischemia/Reperfusion by Activating SIRT3-Mediated Mitophagy and Inhibiting Activation of the NLRP3 Inflammasome in Young Rats

Lyu

Jia

et al. 2020

Oxidative Medicine and Cellular Longevity

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“…First, miR-103 targets BNIP3 (Bcl2/Adenovirus EIB 19 kDa Interacting Protein 3) to mediate late autophagy and relieve H 2 O 2 -induced oxidative stress and pyroptosis ( Wang et al, 2020 ). Second, electrical stimulation affects THP-1 macrophages, activates Sirt3, promotes autophagy, and relieves ROS-induced pyroptosis ( Cong et al, 2020 ). Third, adrenomedullin promotes autophagy and inhibits pyroptosis in testicular stromal cells through the ROS-AMPK-mTOR pathway ( Li et al, 2019 ).…”

Section: Autophagy Is a Double-edged Sword In Oamentioning

confidence: 99%

The P2X7 Receptor in Osteoarthritis

Huang

Bai

2021

Front. Cell Dev. Biol.

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Osteoarthritis (OA) is the most common joint disease. With the increasing aging population, the associated socio-economic costs are also increasing. Analgesia and surgery are the primary treatment options in late-stage OA, with drug treatment only possible in early prevention to improve patients’ quality of life. The most important structural component of the joint is cartilage, consisting solely of chondrocytes. Instability in chondrocyte balance results in phenotypic changes and cell death. Therefore, cartilage degradation is a direct consequence of chondrocyte imbalance, resulting in the degradation of the extracellular matrix and the release of pro-inflammatory factors. These factors affect the occurrence and development of OA. The P2X7 receptor (P2X7R) belongs to the purinergic receptor family and is a non-selective cation channel gated by adenosine triphosphate. It mediates Na+, Ca2+ influx, and K+ efflux, participates in several inflammatory reactions, and plays an important role in the different mechanisms of cell death. However, the relationship between P2X7R-mediated cell death and the progression of OA requires investigation. In this review, we correlate potential links between P2X7R, cartilage degradation, and inflammatory factor release in OA. We specifically focus on inflammation, apoptosis, pyroptosis, and autophagy. Lastly, we discuss the therapeutic potential of P2X7R as a potential drug target for OA.

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“…The relationships and interactions among in ammation, pyroptosis, ROS and autophagy have been widely studied. For example, Cong et al reported that electrical stimulation inhibited pyroptosis in THP-1 macrophages via sirtuin3 activation to promote autophagy and inhibit ROS generation 64 . Recent evidence revealed that lesions of the injured spinal cord led to mitochondrial damage, which contributed to the accumulation of ROS 65 .…”

Section: Discussionmentioning

confidence: 99%

Piperine Attenuates the Inflammatory Response, Oxidative Stress and Pyroptosis to Facilitate Recovery After Spinal Cord Injury via Autophagy Enhancement

Zhang

Huang

et al. 2021

Preprint

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Background: Spinal cord injury (SCI) is a serious injury that can lead to irreversible motor dysfunction and subsequently result in disability and even death. Due to its complicated pathogenic mechanism, there are no effective drug treatments. Piperine, a natural active alkaloid extracted from black pepper, suppressed inflammation in a previous study. The aim of this study was to investigate the therapeutic effect of piperine in a spinal cord injury model.Methods: Spinal cord injury was induced in C57BL/6 mice by clamping the spinal cord with a vascular clip (15 g force; Oscar) for 1 min. Eighty mice were divided randomly into the following four groups: The Sham group (n = 20), the SCI+Vehicle group (n = 20), the SCI+ Piperine group (n = 20), and the SCI+ Piperine+3MA group (n = 20). Before SCI and every 2 days post-SCI, evaluations of the Basso mouse scale (BMS) were performed. On day 14 after SCI, inclined plane tests and footprint analyses were performed. On postoperative day 3, the spinal cord was harvested to assess pyroptosis, reactive oxygen species (ROS), inflammation, and autophagy. Qualitative or quantitative analysis of the components of these potential mechanisms was performed by Western blotting (WB), immunofluorescence (IF), quantitative real-time PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA).Results: Piperine enhanced the functional recovery of spinal cord injury. Additionally, piperine inhibited inflammation, attenuated oxidative stress and pyroptosis, and activated autophagy. However, the effects of piperine on the functional recovery of SCI, ROS-mediated autophagy, inflammation and pyroptosis were reversed by the inhibition of autophagy.Conclusions: Our experiments demonstrated that piperine facilitated the functional recovery of spinal cord injury by inhibiting the inflammatory response, oxidative stress and pyroptosis, which are mediated by the activation of autophagy.

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Electrical stimulation inhibits Val-boroPro-induced pyroptosis in THP-1 macrophages via sirtuin3 activation to promote autophagy and inhibit ROS generation

Cited by 39 publications

References 61 publications

Dexmedetomidine Ameliorates Hippocampus Injury and Cognitive Dysfunction Induced by Hepatic Ischemia/Reperfusion by Activating SIRT3-Mediated Mitophagy and Inhibiting Activation of the NLRP3 Inflammasome in Young Rats

Dexmedetomidine Ameliorates Hippocampus Injury and Cognitive Dysfunction Induced by Hepatic Ischemia/Reperfusion by Activating SIRT3-Mediated Mitophagy and Inhibiting Activation of the NLRP3 Inflammasome in Young Rats

The P2X7 Receptor in Osteoarthritis

Piperine Attenuates the Inflammatory Response, Oxidative Stress and Pyroptosis to Facilitate Recovery After Spinal Cord Injury via Autophagy Enhancement

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