Sevoflurane postconditioning reduces myocardial ischemia reperfusion injury-induced necroptosis by up-regulation of OGT-mediated O-GlcNAcylated RIPK3

Zhang, Jing; Yu, Peng; Hua, Fuzhou; Hu, Yanhui; Fan, Xiao; Q, Liu; Huang, Dan; Deng, Fang; Wei, Gen; Deng, Wei; Ma, Jianyong; Zhu, Wengen; Zhang, Jiru; Yu, Shuchun

doi:10.18632/aging.104146

Cited by 25 publications

(24 citation statements)

References 51 publications

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“…Therefore, Sevoflurane is widely used in anesthesia induction and maintenance. In clinical practice, Sevoflurane has been found to have an protective effect on myocardial ischemia injury (Grishin et al, 2016;Zhang et al, 2017;Zhang et al, 2020), and this finding was supported by relevant studies. However, the mechanism of Sevoflurane against myocardial ischemia has not been determined.…”

Section: Discussionmentioning

confidence: 86%

Sevoflurane Alleviates Myocardial Ischemia Reperfusion Injury by Inhibiting P2X7-NLRP3 Mediated Pyroptosis

Cai

et al. 2021

Front. Mol. Biosci.

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Myocardial ischemia is common in aging population. This study investigates the protective effect of Sevoflurane on myocardial ischemia reperfusion injury (MIRI) and its underlying mechanism. A total of 87 patients with a history of myocardial ischemia who underwent abdominal surgery with Sevoflurane general anesthesia were recruited in the study. The clinical data, blood pressure, heart rate, pressure-rate quotient (PRQ) and rate-pressure product (RPP) were recorded. Serum samples were collected and heart-type fatty acid binding protein (H-FABP), ischemia modified albumin (IMA), interleukin-1β (IL-1β), and interleukin-18 (IL-18) were measured to observe whether Sevoflurane anesthesia had protective effect on myocardium. In addition, MIRI rats and hypoxia/reoxygenation (H/R) injury cell model was established using neonatal rat ventricular myocytes (NRVM). Rats or NRVM were pretreated with sevoflurane for 45min before hypoxia. The mRNA expression of purinergic receptor-7 (P2X7) and NLR family pyrin domain containing 3(NLRP3) were examined. The protein expression of P2X7, NLRP3, apoptosis-associated speck-like protein (ASC), cysteine aspartic acid specific protease-1(Caspase-1), Gasdermin-D (GSDMD), Bcl-2 Associated X Protein (Bax), B-cell lymphoma-2 (Bcl-2) in myocardial tissue and cells were evaluated. The serum contents of IL-1β, IL-18, Malondialdehyde (MDA), Superoxide dismutase (SOD), Lactate dehydrogenase (LDH), Creatine kinase (CK), and Creatine kinase isoenzymes (CK-MB) were measured. The cellular localization and fluorescence intensity of NLRP3 and ASC in cells were detected. It was found that the secretion of IL-1β and IL-18 decreased in the patients. After I45 min/R3h in SD rats and H3h/R1h in NRVM, the protein expressions of P2X7, NLRP3, ASC, Caspase-1 and GSDMD were increased, the release of IL-1β, IL-18, CK, CK-MB, LDH and MDA were increased, and SOD activity was decreased. Sevoflurane treatment inhibited the high expression of P2X7, NLRP3, ASC, Caspase-1 and GSDMD, inhibited the release of LDH, CK,CK-MB and MDA in cells, and improved the activity of SOD, indicating that Sevoflurane alleviated the damage of MIRI of rats and H/R of NRVM, and had myocardial protective effect. Taken together, our study suggests that Sevoflurane inhibited the expression of IL-1β, IL-18 and GSDMD by inhibiting the P2X7-NLRP3 signaling pathway. It reduced the H/R injury of cardiomyocytes and protected the cardiac function by regulating inflammatory reaction and pyroptosis.

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Section: Discussionmentioning

confidence: 86%

Sevoflurane Alleviates Myocardial Ischemia Reperfusion Injury by Inhibiting P2X7-NLRP3 Mediated Pyroptosis

Cai

et al. 2021

Front. Mol. Biosci.

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“…In IBD patients, the levels of O -GlcNAcylation and the expression of OGT, the enzyme promoting O -GlcNAcylation, were all reduced [ 26 ]. Meanwhile, in vivo studies have suggested the promotion of O -GlcNAcylation (such as OGT-transgenic mice) as an effective treatment in mice colitis [ 24 , 27 ]. In contrast to these findings, some studies pointed that the colonic level of O -GlcNAc was increased in CD patients, and suppressing O -GlcNAcylation may protect mice from colitis [ 50 , 51 ].…”

Section: Discussionmentioning

confidence: 99%

“…How does elevated O -GlcNAcylation level alleviates gut inflammation in colitis? Based on limited research, the inhibition of necroptosis by hyper- O -GlcNAcylation-mediated RIPK3 inactivation may be the potential cause [ 21 , 24 ]. Accordingly, we investigated the interaction between hyper- O -GlcNAcylation and necroptotic signal transduction, and the results verified our thoughts.…”

Section: Discussionmentioning

confidence: 99%

“…Whether this phenomenon exist in the process of RIPK3 activation? Various studies have proved that enhanced RIPK3 O -GlcNAcylation can effectively reducing p-RIPK3, inhibiting necroptosis [ 21 , 23 , 24 ]. Mechanically, the cycling of O -GlcNAc modifications is achieved by a single pair of enzymes: O -GlcNAc transferase (OGT) and O -GlcNAcase (OGA).…”

Section: Introductionmentioning

confidence: 99%

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Traditional herbal formula Wu-Mei-Wan alleviates TNBS-induced colitis in mice by inhibiting necroptosis through increasing RIPK3 O-GlcNAcylation

Shao

Cheng

et al. 2021

Chin Med

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Background Accumulating evidence indicated that necroptosis plays an essential role in the pathogenesis of inflammatory bowel disease (IBD). The O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) of necroptotic signal molecule receptor-interacting serine-threonine kinase 3 (RIPK3) was reported to exert a protective effect in gut inflammation. Our recent study suggested traditional Chinese herbal formula Wu-Mei-Wan (WMW) as an effective prescription in mouse colitis. However, the potential mechanisms are not fully understood. Considering the crucial role of necroptosis in the pathogenesis of IBD, therefore, this study was designed to explain whether the anti-colitis effect of WMW is mediated by modulating necroptosis and its related mechanisms. Methods The protective effects of WMW on colitis have been determined by detecting colitis mice body weight, disease activity index (DAI), survival rate and colon length. Colonic inflammation was examined by inflammatory cells infiltration and local cytokines levels. After then, we measured the levels of necroptosis and O-GlcNAcylation. C O-immunoprecipitation experiments were used to address whether elevated O-GlcNAcylation can inhibit necroptotic signal transduction in the treatment of WMW. Finally, the key enzymes in O-GlcNAcylation: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) were examined and molecular docking analysis was used to determine effective natural compounds in the regulation on OGT and OGA activities. Results Our results showed that WMW significantly improved mice body weight, survival rate and colon length, decreased DAI in TNBS-induced colitis. WMW obviously alleviated colonic inflammatory responses with reduced macrophages, neutrophils infiltration and local IL-1β, IL-6, TNF-α and IFN-γ levels. It was found that WMW increased colonic O-GlcNAcylation level and inhibited the activation of RIPK1, RIPK3 and MLKL. Then, further experiments revealed that WMW enhanced OGT activity and suppressed OGA activity, thereby increasing RIPK3 O-GlcNAcylation and inhibiting the binding of RIPK3 and MLKL, which led to the inhibition of necroptosis. Additionally, docking analysis demonstrated that hesperidin, coptisine and ginsenoside Rb1 may exert a major role in the regulation on OGT and OGA activities by WMW. Conclusion Our work demonstrated that WMW can alleviate TNBS-induced colitis in mice by inhibiting necroptosis through increasing RIPK3 O-GlcNAcylation.

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“…Even then, RIPK3 inhibition with GSK'872 or HS-1371 prevented plasma membrane rupture and delayed mPTP opening; the association found with this effect was an increase in manganese superoxide dismutase (MnSOD) expression, suggesting that RIPK3 modulates oxidative stress [251]. On the other hand, SPostC has been shown to reduce RIPK1/RIPK3/MLKL-mediated necroptosis, increase RIPK3 O-GlcNAcylation and diminish necroptosis both in an in vivo model and in isolated hearts subjected to I/R [252].…”

Section: Controlling Necroptosis and Pyroptosismentioning

confidence: 99%

Mitochondrial Quality Control in Cardiac-Conditioning Strategies against Ischemia-Reperfusion Injury

García-Niño

Zazueta

Buelna‐Chontal

et al. 2021

Life

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Mitochondria are the central target of ischemic preconditioning and postconditioning cardioprotective strategies, which consist of either the application of brief intermittent ischemia/reperfusion (I/R) cycles or the administration of pharmacological agents. Such strategies reduce cardiac I/R injury by activating protective signaling pathways that prevent the exacerbated production of reactive oxygen/nitrogen species, inhibit opening of mitochondrial permeability transition pore and reduce apoptosis, maintaining normal mitochondrial function. Cardioprotection also involves the activation of mitochondrial quality control (MQC) processes, which replace defective mitochondria or eliminate mitochondrial debris, preserving the structure and function of the network of these organelles, and consequently ensuring homeostasis and survival of cardiomyocytes. Such processes include mitochondrial biogenesis, fission, fusion, mitophagy and mitochondrial-controlled cell death. This review updates recent advances in MQC mechanisms that are activated in the protection conferred by different cardiac conditioning interventions. Furthermore, the role of extracellular vesicles in mitochondrial protection and turnover of these organelles will be discussed. It is concluded that modulation of MQC mechanisms and recognition of mitochondrial targets could provide a potential and selective therapeutic approach for I/R-induced mitochondrial dysfunction.

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Sevoflurane postconditioning reduces myocardial ischemia reperfusion injury-induced necroptosis by up-regulation of OGT-mediated O-GlcNAcylated RIPK3

Cited by 25 publications

References 51 publications

Sevoflurane Alleviates Myocardial Ischemia Reperfusion Injury by Inhibiting P2X7-NLRP3 Mediated Pyroptosis

Sevoflurane Alleviates Myocardial Ischemia Reperfusion Injury by Inhibiting P2X7-NLRP3 Mediated Pyroptosis

Traditional herbal formula Wu-Mei-Wan alleviates TNBS-induced colitis in mice by inhibiting necroptosis through increasing RIPK3 O-GlcNAcylation

Mitochondrial Quality Control in Cardiac-Conditioning Strategies against Ischemia-Reperfusion Injury

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