title: Panax quinquefolium saponins reduce myocardial hypoxia-reoxygenation injury by inhibiting excessive endoplasmic reticulum stress.
abstract: Excessive endoplasmic reticulum stress (ERS) disrupts protein translation, protein folding, and calcium homeostasis and may contribute to ischemia-reperfusion injury. Saponins extracted from the stems and leaves of Panax quinquefolium (PQS) protect rat myocardium against ischemia-reperfusion injury, but it is not known if suppression of ERS contributes to cardioprotection. Neonatal rat cardiomyocytes were subjected to hypoxia-reoxygenation (H-R) in the presence of PQS or vehicle. Cell injury and apoptosis were assayed by trypan blue exclusion, lactate dehydrogenase activity, and flow cytometry. In addition, reverse transcriptase-polymerase chain reaction and Western blotting were used to examine mRNA and protein expression of the ERS-related proteins glucose-regulated protein 78, calreticulin, CCAAT/enhancer-binding protein homologous protein, and caspase-12, as well as the apoptosis-associated proteins Bax and Bcl-2. We confirmed that PQS protects cardiomyocytes from H-R-induced injury and apoptotic cell death. Furthermore, PQS suppressed H-R-induced excessive ERS, as evidenced by reduced caspase 12 activation and decreased glucose-regulated protein 78, calreticulin, and CCAAT/enhancer-binding protein homologous protein overexpression. These results indicated that PQS could alleviate H-R injury of cardiomyocytes, which would be probably related to inhibiting excessive ERS induced by H-R.
authors.affiliation: Department of Cardiology, Xiyuan Hospital of China Academy of Traditional Chinese Medicine, PLA General Hospital, Beijing, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.forename: Yu-Zhen
authors.initials: YZ
authors.lastname: Li
authors.forename: Xiao-Reng
authors.initials: XR
authors.lastname: Wang
authors.forename: Zhen-Rong
authors.initials: ZR
authors.lastname: Lu
authors.forename: Da-Zhuo
authors.initials: DZ
authors.lastname: Shi
authors.forename: Xiu-Hua
authors.initials: XH
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis; D037282:Calreticulin / Q000378:metabolism; D053454:Caspase 12 / Q000378:metabolism; D002470:Cell Survival; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005434:Flow Cytometry / Q000379:methods; D006360:Heat-Shock Proteins / Q000378:metabolism; D000860:Hypoxia; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism*; D012503:Saponins / Q000378:metabolism*; D051742:Transcription Factor CHOP / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP
chemical_list: D037282:Calreticulin; D053454:Caspase 12; D006360:Heat-Shock Proteins; D007770:L-Lactate Dehydrogenase; D019253:Proto-Oncogene Proteins c-bcl-2; D012503:Saponins; D051742:Transcription Factor CHOP; D051028:bcl-2-Associated X Protein; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP; C079995:Panax quinquefolium saponin