The involvement of endoplasmic reticulum stress in flavonoid-induced protection on cardiac cell death caused by ischaemia/reperfusion.
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.
Kim
Do-Sung
DS
Department of Pharmacology and Institute of Cardiovascular Research, Jeonju, Chonbuk, Republic of Korea.
Kwon
Dae-Young
DY
Kim
Myung-Sunny
MS
Kim
Hye Kyung
HK
Lee
Yong Chul
YC
Park
Seong Ju
SJ
Yoo
Wan Hee
WH
Chae
Soo-Wan
SW
Chung
Myoung-Ja
MJ
Kim
Hyung-Ryong
HR
Chae
Han-Jung
HJ
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
D005419:Flavonoids; D006360:Heat-Shock Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D053148:Caspase 3