Kaempferol protects ischemia/reperfusion-induced cardiac damage through the regulation of endoplasmic reticulum stress.
This study examined whether or not the ER stress and Bcl-2 proteins are linked to the protective effect of kaempferol, a phytoestrogen, on ischemia-reperfusion (I/R)-induced cardiac damage. In order to determine if kaempferol modifies the I/R-induced response in H9c2 cardiac muscle cells, the cells were exposed to kaempferol followed by ischemia 12h/reperfusion 4h. kaempferol had a protective effect on the apoptosis induced by I/R in the cardiac muscle cells. The Kaempferol treatment significantly increased the expression level of the anti-apoptotic protein, Bcl-2, but decreased the level of the pro-apoptotic protein, bax. Kaempferol down-regulated the expressions of the endoplasmic reticulum (ER) stress proteins, GRP78, ATF-6alpha, XBP-2, IRE1-alpha, phosphor-eIF-2alpha and CHOP. In ex vivo-Langendorff experiment, the kaempferol treatment regulated the expression of ER stress proteins-CHOP and GRP78. The kaempferol also improved the post-ischemic LVEDP and LVDP significantly after 20, 30, 40 and 50 min of reperfusion compared with the untreated control hearts, which shows that kaempferol offers protection against I/R-associated cardiac dysfunction.
Kim
Do-Sung
DS
Department of Pharmacology and Clinical Trial Center, Medical School, Chonbuk National University, Jeonju, Chonbuk, Republic of Korea.
Ha
Ki-Chan
KC
Kwon
Dae-Young
DY
Kim
Myung-Sunny
MS
Kim
Hyung-Ryong
HR
Chae
Soo-Wan
SW
Chae
Han-Jung
HJ
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000276:immunology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000276:immunology; D006360:Heat-Shock Proteins / Q000378:metabolism; D066298:In Vitro Techniques; D044949:Kaempferols / Q000494:pharmacology*; D018832:Molecular Chaperones / Q000378:metabolism; D009124:Muscle Proteins / Q000096:biosynthesis* / Q000276:immunology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000276:immunology / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D051742:Transcription Factor CHOP / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP
D002316:Cardiotonic Agents; D006360:Heat-Shock Proteins; D044949:Kaempferols; D018832:Molecular Chaperones; D009124:Muscle Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051742:Transcription Factor CHOP; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP; C006552:kaempferol