Astragaloside IV Improved Intracellular Calcium Handling in Hypoxia-Reoxygenated Cardiomyocytes via the Sarcoplasmic Reticulum Ca²⁺-ATPase

Abstract

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.

Beta-1-Adrenergic Receptors Mediate Nrf2-HO-1-HMGB1 Axis Regulation to Attenuate Hypoxia/Reoxygenation-Induced Cardiomyocytes Injury in Vitro

“…Otherwise, HO-1 has been further demonstrated to be induced by dobutamine and inhibit HMGB1 release during myocardial I/R injury [11]. Importantly, cultured neonatal cardiomyocytes may present with a very stable phenotype and the contractile profile of cultured neonatal cardiomyocytes during H/R has been proved to be comparable with that of in situ adult hearts during I/R [26][27][28][29].…”

Effects of Astragaloside IV on Action Potentials and Ionic Currents in Guinea-Pig Ventricular Myocytes

“…Recent researches have suggested that AS-IV might protect from cardiomyopathy via diverse effects upon a variety of intracellular signaling pathways, including the activation of Src/mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway, 22) inhibiting tumor growth factor (TGF)-β1 23) and ERK1/2 signaling pathways, 24) upregulating superoxide dismutase-1 levels, 3,25) antioxidative and nitric oxide-inducing pathway, 26) and improving intracellular calcium handling. 27,28) The aim of our study is to clarify the basic electrophysiological effects of AS-IV on cardiac myocytes, and we have found that AS-IV prolonged APd, and decreased I K and I CaL in guinea-pig cardiac myocytes. The action potential is formed by multiple ion currents gated by different ion channels.…”

Astragaloside IV Stimulates Angiogenesis and Increases Hypoxia-Inducible Factor-1α Accumulation via Phosphatidylinositol 3-Kinase/Akt Pathway

“…In isolated aortic rings, astragaloside IV-induced vasodilation was attributed to the endothelium-dependent nitric oxide-cGMP pathway, in both normal and hypertensive rats, and inhibition of vessel contraction was attributed to blockage of calcium influx (Zhang et al, 2006a(Zhang et al, , 2007. In hypoxia and reoxygenation-induced injury in vitro, astragaloside IV demonstrated a protective effect by normalization of the sarcoplasmic reticulum Ca 2ϩ pump expression and prevention of depression in Ca 2ϩ handling by the sarcoplasmic reticulum (Xu et al, 2008b). The improvement by astragaloside IV of sarcoplasmic reticulum Ca 2ϩ pump function was also confirmed by its action in isoproterenol-induced myocardial injury in vivo, for which the result indicated that astragaloside IV improved cardiac function by preventing changes of Ca 2ϩ -ATPase activity and Ser16-phosphorylated phospholamban protein expression (Xu et al, 2007).…”