title: Exogenous Hydrogen Sulfide Attenuates High Glucose-Induced Cardiotoxicity by Inhibiting NLRP3 Inflammasome Activation by Suppressing TLR4/NF-κB Pathway in H9c2 Cells.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Cardiology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Zena
authors.initials: Z
authors.lastname: Huang
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhuang
authors.forename: Chuli
authors.initials: C
authors.lastname: Xie
authors.forename: Xun
authors.initials: X
authors.lastname: Hu
authors.forename: Xiaobian
authors.initials: X
authors.lastname: Dong
authors.forename: Yue
authors.initials: Y
authors.lastname: Guo
authors.forename: Shaofen
authors.initials: S
authors.lastname: Li
authors.forename: Xinxue
authors.initials: X
authors.lastname: Liao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D066126:Cardiotoxicity / Q000378:metabolism*; D002460:Cell Line; D019610:Cytoprotection / Q000187:drug effects; D020868:Gene Silencing / Q000187:drug effects; D005947:Glucose / Q000633:toxicity*; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D058847:Inflammasomes / Q000378:metabolism*; D007249:Inflammation / Q000473:pathology; D008954:Models, Biological; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: D058847:Inflammasomes; D016328:NF-kappa B; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C573346:Nlrp3 protein, rat; D051197:Toll-Like Receptor 4; D005947:Glucose; D006862:Hydrogen Sulfide