title: The involvement of endoplasmic reticulum stress in flavonoid-induced protection on cardiac cell death caused by ischaemia/reperfusion.
abstract: OBJECTIVE
  We have investigated whether endoplasmic reticulum stress and Bcl-2 proteins were linked to the protective effect exerted by flavonoids on ischaemia/reperfusion-induced cardiac damage.
  
  
  METHODS
  Cell viability and immunoblotting were performed.
  
  
  RESULTS
  H9c2 cardiac muscle cells were exposed to flavonoids such as biochanin A, daidzein, genistein, luteolin, quercetin and rutin, followed by ischaemia 12 h/reperfusion 4 h. The flavonoids protected against cell death induced by ischaemia/reperfusion. Flavonoid treatment significantly increased the expression level of the anti-apoptotic protein, Bcl-2, but decreased that of the proapoptotic protein, Bax. The flavonoids down-regulated the expression levels of endoplasmic reticulum stress proteins, glucose-regulated protein-78, activating transcription factor 6alpha, X-box binding protein 1, inositol-requiring protein-1, phosphor-eukaryotic initiation factor 2alpha, and C/EBP-homologous protein.
  
  
  CONCLUSIONS
  This study suggested that the protective mechanisms of flavonoids included regulation of Bcl-2/Bax proteins as well as the endoplasmic reticulum stress proteins.
authors.affiliation: Department of Pharmacology and Institute of Cardiovascular Research, Jeonju, Chonbuk, Republic of Korea.
authors.forename: Do-Sung
authors.initials: DS
authors.lastname: Kim
authors.forename: Dae-Young
authors.initials: DY
authors.lastname: Kwon
authors.forename: Myung-Sunny
authors.initials: MS
authors.lastname: Kim
authors.forename: Hye Kyung
authors.initials: HK
authors.lastname: Kim
authors.forename: Yong Chul
authors.initials: YC
authors.lastname: Lee
authors.forename: Seong Ju
authors.initials: SJ
authors.lastname: Park
authors.forename: Wan Hee
authors.initials: WH
authors.lastname: Yoo
authors.forename: Soo-Wan
authors.initials: SW
authors.lastname: Chae
authors.forename: Myoung-Ja
authors.initials: MJ
authors.lastname: Chung
authors.forename: Hyung-Ryong
authors.initials: HR
authors.lastname: Kim
authors.forename: Han-Jung
authors.initials: HJ
authors.lastname: Chae
mesh_terms: D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005419:Flavonoids / Q000494:pharmacology* / Q000627:therapeutic use; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D006801:Humans; D015151:Immunoblotting; D008954:Models, Biological; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis
chemical_list: D005419:Flavonoids; D006360:Heat-Shock Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D053148:Caspase 3