Astragaloside IV Improved Intracellular Calcium Handling in Hypoxia-Reoxygenated Cardiomyocytes via the Sarcoplasmic Reticulum Ca2+-ATPaseXu X.-L.a · Chen X.-J.c · Ji H.a · Li P.b · Bian Y.-Y.b · Yang D.c · Xu J.-D.c · Bian Z.-P.c · Zhang J.-N.c
aDepartment of Pharmacology, China Pharmaceutical University, bKey Laboratory of Modern Chinese Medicines, Department of Pharmacognosy, China Pharmaceutical University, and cResearch Institute of Cardiovascular Disease, First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China
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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.
© 2008 S. Karger AG, Basel
- Kang SM, Lim S, Song H, Chang W, Lee S, Bae SM, Chung JH, Lee H, Kim HG, Yoon DH, Kim TW, Jang Y, Sung JM, Chung NS, Hwang KC: Allopurinol modulates reactive oxygen species generation and Ca2+ overload in ischemia-reperfused heart and hypoxia-reoxygenated cardiomyocytes. Eur J Pharmacol 2006;535:212–219.
- Zucchi R, Ronca F, Ronca-Testoni S: Modulation of sarcoplasmic reticulum function: a new strategy in cardioprotection? Pharmacol Ther 2001;89:47–65.
- Gianni D, Chan J, Gwathmey JK, del Monte F, Hajjar RJ: SERCA2a in heart failure: role and therapeutic prospects. J Bioenerg Biomembr 2005;37:375–380.
- Dash R, Frank KF, Carr AN, Moravec CS, Kranias EG: Gender influences on sarcoplasmic reticulum Ca2+ handling in failing human myocardium. J Mol Cell Cardiol 2001;33:1345–1353.
- Schmidt U, Hajjar RJ, Helm PA, Kim CS, Doye AA, Gwathmey JK: Contribution of abnormal sarcoplasmic reticulum ATPase activity to systolic and diastolic dysfunction in human heart failure. J Mol Cell Cardiol 1998;30:1929–1937.
- Muller OJ, Lange M, Rattunde H, Lorenzen HP, Muller M, Frey N, Bittner C, Simonides W, Katus HA, Franz WM: Transgenic rat hearts overexpressing SERCA2a show improved contractility under baseline conditions and pressure overload. Cardiovasc Res 2003;59:380–389.
- Han L, Chen K: Progress of experimental pharmacologic study on the effect of Astragaus on the cardiacvascular system. Zhongguo Zhong Xi Yi Jie He Za Zhi 2000;20:234–237.
- Miller AL: Botanical influences on cardiovascular disease. Altern Med Rev 1998;3:422–431.
- Sun HY, Wang NP, Kerendi F, Halkos M, Kin H, Guyton RA, Vinten-Johansen J, Zhao ZQ: Hypoxic postconditioning reduces cardiomyocyte loss by inhibiting ROS generation and intracellular Ca2+ overload. Am J Physiol Heart Circ Physiol 2005;288:H1900–H1908.
- Zhou JY, Fan Y, Kong JL, Wu DZ, Hu ZB: Effects of components isolated from Astragalus membranaceus Bunge on cardiac function injured by myocardial ischemia reperfusion in rats. Zhongguo Zhong Yao Za Zhi 2000;25:300–302.
- Zhang WD, Chen H, Zhang C, Liu RH, Li HL, Chen HZ: Astragaloside IV from Astragalus membranaceus shows cardioprotection during myocardial ischemia in vivo and in vitro. Planta Med 2006;72:4–8.
- Chlopcikova S, Psotova J, Miketova P: Neonatal rat cardiomyocytes – a model for the study of morphological, biochemical and electrophysiological characteristics of the heart. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2001;145:49–55.
- Rui T, Feng Q, Lei M, Peng T, Zhang J, Xu M, Abel ED, Xenocostas A, Kvietys PR: Erythropoietin prevents the acute myocardial inflammatory response induced by ischemia/reperfusion via induction of AP-1. Cardiovasc Res 2005;65:719–727.
- Chanalaris A, Sun Y, Latchman DS, Stephanou A: SAG attenuates apoptotic cell death caused by simulated ischaemia/reoxygenation in rat cardiomyocytes. J Mol Cell Cardiol 2003;35:257–264.
- Chen XJ, Bian ZP, Lu S, Xu JD, Gu CR, Yang D, Zhang JN: Cardiac protective effect of Astragalus on viral myocarditis mice: comparison with Perindopril. Am J Chin Med 2006;34:493–502.
- Ozaki H, Zaizen H, Kiyosue T, Nasu M, Arita M: Effect of bepridil on intracellular calcium concentration and contraction in cultured rat ventricular myocytes. J Cardiovasc Pharmacol 1999;33:492–499.
- Ren J, Porter JE, Wold LE, Aberle NS, Muralikrishnan D, Haselton JR: Depressed contractile function and adrenergic responsiveness of cardiac myocytes in an experimental model of Parkinson disease, the MPTP-treated mouse. Neurobiol Aging 2004;25:131–138.
- Chen XJ, Meng D, Feng L, Bian YY, Li P, Yang D, Cao KJ, Zhang JN: Protective effect of astragalosides on myocardial injury by isoproterenol in SD rats. Am J Chin Med 2006;34:1015–1025.
- Larsen JS, Kjeldsen K: Quantification in crude homogenates of rat myocardial Na+, K+- and Ca2+-ATPase by K+ and Ca2+-dependent pNPPase: age-dependent changes. Basic Res Cardiol 1995;90:323–331.
- Lu S, Zhang J, Yang D: Effects of Astragaloside in treating myocardial injury and myocardial Sarco/Endoplasmic Ca2+-ATPase of viral myocarditis mice. Zhongguo Zhong Xi Yi Jie He Za Zhi 1999;19:672–674.
- Meng D, Chen XJ, Bian YY, Li P, Yang D, Zhang JN: Effect of astragalosides on intracellular calcium overload in cultured cardiac myocytes of neonatal rats. Am J Chin Med 2005;33:11–20.
- O’Brien PJ, Smith DE, Knechtel TJ, Marchak MA, Pruimboom-Brees I, Brees DJ, et al: Cardiac troponin I is a sensitive, specific biomarker of cardiac injury in laboratory animals. Lab Anim 2006;40:153–171.
- Zhou S, Shao W, Zhang W: Clinical study of Astragalus injection plus ligustrazine in protecting myocardial ischemia reperfusion injury. Zhongguo Zhong Xi Yi Jie He Za Zhi 2000;20:504–507.
- Li ZP, Cao Q: Effects of astragaloside IV on myocardial calcium transport and cardiac function in ischemic rats. Acta Pharmacol Sin 2002;23:898–904.
- Bassani JW, Bassani RA, Bers DM: Relaxation in rabbit and rat cardiac cells: species-dependent differences in cellular mechanisms. J Physiol 1994;476:279–293.
- Yang Z, Steele DS: Effects of cytosolic ATP on Ca2+ sparks and SR Ca2+ content in permeabilized cardiac myocytes. Circ Res 2001;89:526–533.
- Takeo S, Elmoselhi AB, Goel R, Sentex E, Wang J, Dhalla NS: Attenuation of changes in sarcoplasmic reticular gene expression in cardiac hypertrophy by propranolol and verapamil. Mol Cell Biochem 2000;213:111–118.
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