30 August 2018 : Animal Research
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
Qian Lei1AE*, Tao Yi1BCD, Can Chen1FGDOI: 10.12659/MSM.908529
Med Sci Monit 2018; 24: ANS6044-6052
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, Western blot, and LDH assay kit.
RESULTS: Suppression of oxidative stress by NAC reduced NF-κB and GSDMD activation and increased pyroptosis, characterized by LDH release and NLRP3 inflammasome activation in H9C2 cells under OGD. Moreover, inhibition of NF-κB activation reduced GSDMD transcription and activation and NLRP3 inflammasome-mediated pyroptosis of H9C2 cells under OGD.
CONCLUSIONS: We demonstrated that the NF-κB-GSDMD axis functioned as a bridge between oxidative stress and NLRP3 inflammasome-mediated cardiomyocyte pyroptosis. Our findings provide important insight into the mechanism of myocardial infarction-related ventricular remodeling.
Keywords: Inflammasomes, NF-kappa B
Editorial
01 May 2022 : Editorial
Editorial: Cardiovascular Complications at One Year After SARS-CoV-2 Infection are Independent of Underlying Cardiovascular Risk Factors or Severity of COVID-19DOI: 10.12659/MSM.937048
Med Sci Monit 2022; 28:e937048
SARS-CoV-2/COVID-19
24 May 2022 : Clinical Research
Screening for SARS-CoV-2 Infection in Students at the Medical University of Warsaw, Poland Between November...Med Sci Monit In Press; DOI: 10.12659/MSM.936962
04 May 2022 : Clinical Research
Effects of Wearing Face Masks on Exercise Capacity and Ventilatory Anaerobic Threshold in Healthy Subjects ...Med Sci Monit In Press; DOI: 10.12659/MSM.936069
27 May 2022 : Clinical Research
Factors Associated with Falls During Hospitalization for Coronavirus Disease 2019 (COVID-19)Med Sci Monit 2022; 28:e936547
25 May 2022 : Meta-Analysis
Effect of the COVID-19 Pandemic on Serum Vitamin D Levels in People Under Age 18 Years: A Systematic Review...Med Sci Monit 2022; 28:e935823
In Press
27 May 2022 : Clinical Research
Prognostic Significance of Preoperative Integrated Liver Inflammatory Score in Patients with Hepatocellular...Med Sci Monit In Press; DOI: 10.12659/MSM.937005
25 May 2022 : Review article
Narrative Review of the Mechanism of Hip Prosthesis Dislocation and Methods to Reduce the Risk of DislocationMed Sci Monit In Press; DOI: 10.12659/MSM.935665
24 May 2022 : Clinical Research
Remimazolam Tosilate Sedation with Adjuvant Sufentanil in Chinese Patients with Liver Cirrhosis Undergoing ...Med Sci Monit In Press; DOI: 10.12659/MSM.936580
24 May 2022 : Clinical Research
Screening for SARS-CoV-2 Infection in Students at the Medical University of Warsaw, Poland Between November...Med Sci Monit In Press; DOI: 10.12659/MSM.936962
Most Viewed Current Articles
30 Dec 2021 : Clinical Research
Retrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...DOI :10.12659/MSM.935379
Med Sci Monit 2021; 27:e935379
08 Mar 2022 : Review article
A Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Man...DOI :10.12659/MSM.936292
Med Sci Monit 2022; 28:e936292
01 Nov 2020 : Review article
Long-Term Respiratory and Neurological Sequelae of COVID-19DOI :10.12659/MSM.928996
Med Sci Monit 2020; 26:e928996
01 Jan 2022 : Editorial
Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...DOI :10.12659/MSM.935952
Med Sci Monit 2022; 28:e935952