title: Sirtuin 6 is essential for sodium sulfide-mediated cytoprotective effect in ischemia/reperfusion-stimulated brain endothelial cells.
abstract: BACKGROUND
  Our recent data demonstrated that hydrogen sulfide (H2S), the third gaseous transmitter, had a protective effect on stroke. The purpose of this study was to investigate the protective effect of H2S in oxygen glucose deprivation and reperfusion (OGD/R)-stimulated brain endothelial cells and its association with sirtuin 6 (SIRT6).
  
  
  METHODS
  Cultured bEnd.3 brain endothelial cells were exposed to OGD/R. The effects of sodium sulfide (Na2S, an exogenous H2S donor) on cell death, lactate dehydrogenase release, intracellular reactive oxygen species (ROS) production, superoxide dismutase (SOD) and catalase (CAT) activities, H2S level, cystathionine γ-lyase (CSE) expression, and sirtuin 6 (SIRT6) expression/activity were tested to elucidate the protective mechanisms of H2S.
  
  
  RESULTS
  Application of Na2S concentration dependently reduced OGD/R-induced cell death, accompanying with decreasing intracellular ROS production and increasing activities of SOD and CAT. In addition, Na2S also enhanced H2S level and CSE expression associated with upregulation of SIRT6 expression and activity in OGD/R-stimulated brain endothelial cells, whereas CSE inhibitor DL-propargylglycine further deteriorated the decrease of SIRT6 expression and activity as well as the reduction of H2S level and CSE expression caused by OGD/R. Furthermore, SIRT6 knockdown abolished Na2S-mediated CSE expression and cytoprotection action in OGD/R-stimulated cells.
  
  
  CONCLUSIONS
  Na2S protected brain endothelial cells against simulated ischemic injury through SIRT6-dependent mechanisms.
authors.affiliation: Department of Pharmacology, Anhui Medical University, Hefei, China; Department of Anesthesiology, The Third Affiliated Hospital of Anhui Medical University, Hefei, China.
authors.forename: Youyang
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Pharmacy, The Third Affiliated Hospital of Anhui Medical University, Hefei, China.
authors.forename: Ruilin
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital of Anhui Medical University, Hefei, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital of Anhui Medical University, Hefei, China. Electronic address: ihxy816@sina.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Luo
authors.affiliation: Department of Pharmacology, Anhui Medical University, Hefei, China.
authors.forename: Zhiwu
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D002545:Brain Ischemia / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D002374:Catalase / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D015687:Cell Hypoxia; D002460:Cell Line; D003542:Cystathionine gamma-Lyase / Q000037:antagonists & inhibitors / Q000378:metabolism; D019610:Cytoprotection; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005740:Gases; D005947:Glucose / Q000172:deficiency; D006862:Hydrogen Sulfide / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects*; D034622:RNA Interference; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism*; D013440:Sulfides / Q000378:metabolism / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D014162:Transfection
chemical_list: D000975:Antioxidants; D004791:Enzyme Inhibitors; D005740:Gases; D017382:Reactive Oxygen Species; D013440:Sulfides; D002374:Catalase; D013482:Superoxide Dismutase; C501860:Sirt6 protein, mouse; D037761:Sirtuins; D003542:Cystathionine gamma-Lyase; D005947:Glucose; C033479:sodium sulfide; D006862:Hydrogen Sulfide
keywords: Hydrogen sulfide; brain endothelial cells; cerebral ischemia/reperfusion; sirtuin 6