NF-κB-Gasdermin D (GSDMD) Axis Couples Oxidative Stress and NACHT, LRR and PYD Domains-Containing Protein 3 (NLRP3) Inflammasome-Mediated Cardiomyocyte Pyroptosis Following Myocardial Infarction

Medical Science Monitor : International Medical Journal of Experimental and Clinical Research
Qian LeiCan Chen

Abstract

BACKGROUND Pyroptosis and oxidative stress play pivotal roles in cardiomyocyte loss after myocardial infarction. NF-κB is associated with oxidative stress and gasdermin D (GSDMD), the effector molecule of pyroptosis. However, the exact relationship between oxidative stress and cardiomyocyte pyroptosis remains unknown. MATERIAL AND METHODS We measured inflammasome-mediated cardiomyocyte pyroptosis in vivo via membrane pore formation, lactate dehydrogenase (LDH) release, and expression of caspase-1, cleaved caspase-1, NACHT, LRR and PYD domains-containing protein 3 (NLRP3), and apoptosis-associated speck-like protein containing a CARD (ASC). Furthermore, we induced pyroptosis in vitro by oxygen-glucose deprivation (OGD) in H9C2 cells. NLRP3 inflammasome-mediated pyroptosis was confirmed by LDH assay kit and Western blot. Oxidative stress was evaluated by reactive oxygen species (ROS) and superoxide dismutase (SOD) activity. We suppressed oxidative stress with N-acetyl-cysteine (NAC) and measured subsequent changes to the NF-κB-GSDMD axis and pyroptosis by LDH assay kit and Western blot. Then, we inhibited NF-κB activation with pyrrolidine dithiocarbamate (PDTC) and measured changes to GSDMD activity and pyroptosis by qRT-PCR, Wes...Continue Reading

Citations

Aug 24, 2019·American Journal of Physiology. Heart and Circulatory Physiology·Takeshi SuetomiJoan Heller Brown
Jul 13, 2019·Frontiers in Aging Neuroscience·Carolina OsorioAdonis Sfera
Jan 19, 2021·Medicinal Research Reviews·Carolina PellegriniVincenzo Calderone
Apr 19, 2020·International Immunopharmacology·Abdullah Al MamunJian Xiao
Feb 26, 2020·Pharmacology & Therapeutics·Anita A PinarChrishan S Samuel
Mar 18, 2021·The Kaohsiung Journal of Medical Sciences·Ji-Guo WangJing Zhang
Mar 23, 2021·Frontiers in Cell and Developmental Biology·Xi-Min HuKun Xiong
Dec 21, 2018·International Immunopharmacology·Chang JiaMaoping Chu
May 28, 2021·Journal of Molecular and Cellular Cardiology·Yu BianBaofeng Yang
Jun 29, 2021·Frontiers in Cell and Developmental Biology·Xun WuChengming Fan
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Jul 30, 2021·Cellular & Molecular Immunology·Yi HuangRongbin Zhou
Jan 28, 2022·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Wei YuanHaichen Wang
Dec 9, 2021·Molecular Medicine Reports·Yongxing LiYamin Hu
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Jan 29, 2022·Apoptosis : an International Journal on Programmed Cell Death·Xiaorong XinYanrong Li

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Methods Mentioned

BETA
transmission electron microscopy
immunoprecipitation
gene knockdown

Software Mentioned

GraphPad
Gel
LightCycler 480
GraphPad Prism
- Pro Analyzer

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