SIRT1 agonism modulates cardiac NLRP3 inflammasome through pyruvate dehydrogenase during ischemia and reperfusion.
Ying Han,Weiju Sun,Di Ren,Jingwen Zhang,Zhibin He,Julia Fedorova,Xiaodong Sun,Fang Han,Ji Li +8 more
TLDR
Results indicate that SIRT1 agonism can inhibit activation of NLRP3 inflammasome via Akt-dependent metabolic regulation during ischemic insults by I/R.Abstract:
Nucleotide-binding oligomerization domain-Like Receptor with a Pyrin domain 3 (NLRP3) inflammasome was emerged as a marker of metabolic dysregulation. We revealed that age-related Sirtuin-1 (SIRT1) modulates cardiac metabolism that medicated inflammatory response during ischemia and reperfusion (I/R) stress. We hypothesize that SIRT1 attenuates NLRP3 inflammasome-dependent inflammation and pyroptosis during myocardial I/R through metabolic modulation. C57BL/6J wild type (WT) mice, inducible cardiomyocyte specific SIRT1 knockout (icSIRT1 KO) and inducible cardiomyocyte specific PDH E1α knockout (icPDH E1α KO) mice were subjected to ligation and release of left anterior descending coronary artery for in vivo regional I/R models. The echocardiography measurement demonstrated that SIRT1 agonist SRT1720 (30 μg/g) improved cardiac systolic function during 45 min of ischemia and 6 h of reperfusion in C57BL/6J WT mice. The biochemical analysis showed that I/R triggered activation of cardiac pyruvate dehydrogenase (PDH), while SIRT1 agonist SRT1720 inhibited I/R-induced PDH activity and reduced production of reactive oxygen species (ROS) during myocardial I/R. Moreover, SRT1720 regulates PDH-related glucose oxidative metabolism to reduce NLRP3 inflammasome activation and pyroptosis in an Akt signaling dependent manner during I/R. Furthermore, an impaired Akt signaling was observed in icSIRT1 KO versus SIRT1fox/flox mice under I/R stress. Intriguingly, we observed lower levels of ROS generation, decreased NLRP3 levels and less pyroptosis occurred in the icPDH E1α KO versus PDH E1αflox/flox hearts during I/R. Taken together, the results indicate that SIRT1 agonism can inhibit activation of NLRP3 inflammasome via Akt-dependent metabolic regulation during ischemic insults by I/R.read more
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Regulation of SIRT1 and Its Roles in Inflammation
TL;DR: The mechanisms that regulate SIRT1 expression, including upstream activators and suppressors that operate on the transcriptional and post-transcriptional levels, are summarized and the potential for Sirt1-based therapeutics for inflammatory diseases is highlighted.
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Puerarin protects against myocardial ischemia/reperfusion injury by inhibiting inflammation and the NLRP3 inflammasome: The role of the SIRT1/NF-κB pathway
Zi-Kuan Wang,Ruirui Chen,Jing-Hua Li,Jing-Yuan Chen,Wei Li,Niu Xiaolin,Fang-Fang Wang,Jing Wang,Jing-Xiao Yang +8 more
TL;DR: Puerarin protected against MI/R injury by inhibiting inflammatory responses probably via the SIRT1/NF-κB pathway, and inhibition of the NLRP3 inflammasome was also involved in puerarin-induced cardioprotective effects, suggesting that puer Karin may be a novel candidate for the treatment of ischemic heart disease.
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Melatonin Attenuates Neuroinflammation by Down-Regulating NLRP3 Inflammasome via a SIRT1-Dependent Pathway in MPTP-Induced Models of Parkinson’s Disease
Ran Zheng,Yang Ruan,Yi-Qun Yan,Zhi-Hao Lin,Nai-Jia Xue,Yaping Yan,Jun Tian,Xinzhen Yin,Jiali Pu,Baorong Zhang +9 more
TL;DR: In this article, the anti-inflammatory effects of melatonin were investigated in vitro and in vivo, using 1-methyl-4-phenylpyridinium (MPP+)-simulated BV2 and primary microglia cell models, with or without melatonin treatment.
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Nutraceutical Strategies for Suppressing NLRP3 Inflammasome Activation: Pertinence to the Management of COVID-19 and Beyond.
Mark F. McCarty,Simon Bernard Iloki Assanga,Lidianys Lewis Lujan,James H. O'Keefe,James J. DiNicolantonio +4 more
TL;DR: In this article, a consideration of the molecular biology underlying inflammasome priming and activation enables the prediction that a range of nutraceuticals may have clinical potential for suppressing inflammmasome activity-antioxidants including phycocyanobilin, phase 2 inducers, melatonin, and N-acetylcysteine.
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SIRT1 Promotes M2 Microglia Polarization via Reducing ROS-Mediated NLRP3 Inflammasome Signaling After Subarachnoid Hemorrhage
TL;DR: In this paper, the effects of SIRT1 on microglial polarization and the underlying molecular mechanisms after subarachnoid hemorrhage (SAH) have not been fully illustrated.
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