Exogenous Hydrogen Sulfide Attenuates High Glucose-Induced Cardiotoxicity by Inhibiting NLRP3 Inflammasome Activation by Suppressing TLR4/NF-κB Pathway in H9c2 Cells
Autor: | Xiao-bian Dong, Shaofen Li, Xinxue Liao, Zena Huang, Chuli Xie, Yue Guo, Xiaodong Zhuang, Xun Hu |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Physiology Inflammasomes Inflammation Apoptosis Biology Models Biological Cell Line 03 medical and health sciences 0302 clinical medicine NLR Family Pyrin Domain-Containing 3 Protein medicine Animals Myocytes Cardiac Viability assay Gene Silencing Hydrogen Sulfide Cytotoxicity NF-kappa B Inflammasome Cardiotoxicity Cell biology Rats Toll-Like Receptor 4 030104 developmental biology Glucose Biochemistry Cell culture Cytoprotection 030220 oncology & carcinogenesis TLR4 medicine.symptom Signal transduction medicine.drug Signal Transduction |
Zdroj: | Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology. 40(6) |
ISSN: | 1421-9778 |
Popis: | Background/Aims: This study aimed to investigate whether exogenous hydrogen sulfide (H2S) confered cardiac protection against high glucose (HG)-induced injury by inhibiting NLRP3 inflammasome activation via a specific TLR4/NF-κB pathway. Methods: H9c2 cardiac cells were exposed to 33 mM glucose for 24 h to induce HG-induced cytotoxicity. The cells were pretreated with NaHS (a donor of H2S) before exposure to HG. Cell viability, cell apoptosis, intracellular reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and TLR4, NF-κB, NLRP3 inflammasome, IL-1β, IL-18 and caspase-3 expression were measured by standard methods. Results: H2S attenuated HG-induced cell apoptosis, ROS expression and loss of MMP and reduced the expression of NLRP3, ASC, pro-caspase-1, caspase-1, IL-1β, IL-18 and caspase-3. In addition, H2S inhibited the HG-induced activation of TLR4 and NF-κB. Furthermore, NLRP3 inflammasome activation was regulated by the TLR4 and NF-κB pathway. Conclusion: The present study demonstrated for the first time that H2S appears to suppress HG-induced cardiomyocyte inflammation and apoptosis by inhibiting the TLR4/NF-κB pathway and its downstream NLRP3 inflammasome activation. Thus H2S might possess potential in the treatment of diabetic cardiomyopathy. |
Databáze: | OpenAIRE |
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