Astragaloside IV improved intracellular calcium handling in hypoxia-reoxygenated cardiomyocytes via the sarcoplasmic reticulum Ca-ATPase.
Although astragaloside IV, a saponin isolated from Astragalus membranaceus, has been shown to protect the myocardium against ischemia/reperfusion injury, its effect on the status of sarcoplasmic reticulum (SR) Ca2+ transport in the injured myocardium remains largely unknown. In this study, we investigated whether in cultured cardiomyocytes subjected to hypoxia and reoxygenation (H/R) administration of astragaloside IV during H/R attenuates the myocardial cell injury and prevents changes in Ca2+ handling activities and gene expression of SR Ca2+ pump. Cultured cardiomyocytes from neonatal rats were exposed to 6 h of hypoxia followed by 3 h of reoxygenation. Myocyte injury was determined by the release of cardiac troponin I in supernatant. Astragaloside IV significantly inhibited cardiac troponin I release after H/R in a dose-dependent manner. The diastolic [Ca2+]i measured with Fura-2/AM was significantly increased after reoxygenation. Astragaloside IV prevented the rise of diastolic [Ca2+]i and the depression of caffeine-induced Ca2+ transients caused by H/R. Furthermore, the observed depressions in SR Ca2+-ATPase activity as well as the mRNA and protein expression of SR Ca2+-ATPase in hypoxic-reoxygenated cardiomyocytes were attenuated by astragaloside IV treatment. These results suggest that the beneficial effect of astragaloside IV in H/R-induced injury may be related to normalization of SR Ca2+ pump expression and, thus, may prevent the depression in SR Ca2+ handling.
Xu
Xiao-Le
XL
Department of Pharmacology, China Pharmaceutical University, Nanjing, PR China.
Chen
Xiang-Jian
XJ
Ji
Hui
H
Li
Ping
P
Bian
Yun-Yun
YY
Yang
Di
D
Xu
Jin-Dan
JD
Bian
Zhi-Ping
ZP
Zhang
Ji-Nan
JN
D000818:Animals; D000831:Animals, Newborn; D027885:Astragalus propinquus / Q000737:chemistry; D002118:Calcium / Q000378:metabolism*; D015687:Cell Hypoxia; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005456:Fluorescent Dyes / Q000378:metabolism; D016257:Fura-2 / Q000031:analogs & derivatives / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D012503:Saponins / Q000008:administration & dosage / Q000494:pharmacology*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000187:drug effects* / Q000378:metabolism; D014315:Triterpenes / Q000008:administration & dosage / Q000494:pharmacology*
D005456:Fluorescent Dyes; D012333:RNA, Messenger; D012503:Saponins; D014315:Triterpenes; C049925:fura-2-am; C052064:astragaloside A; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D010100:Oxygen; D002118:Calcium; D016257:Fura-2