Muller A, Zuidwijk M J, Simonides W S, van Hardeveld C
Laboratory for Physiology, Institute for Cardiovascular Research, Vrije Universiteit, Amsterdam, The Netherlands.
Am J Physiol. 1997 Apr;272(4 Pt 2):H1876-85. doi: 10.1152/ajpheart.1997.272.4.H1876.
Decreased expression of the cardiac slow-twitch sarcoplasmic reticulum Ca2+-adenosinetriphosphatase (SERCA2), a major determinant of Ca2+ homeostasis, contributes to the abnormal intracellular Ca2+ handling in the failing heart. We investigated the contractility dependence of the effects of norepinephrine (NE) and thyroid hormone (T3) on SERCA2 expression in cultured neonatal heart cells under serum-free conditions. NE and T3 are associated with pathological and physiological forms of hypertrophy, respectively, whereas both hormones increase contractility. In contracting cultures, T3 increased SERCA2 protein and mRNA levels by 35 and 110%, respectively. The same stimulatory effects of T3 on SERCA2 expression were found in contraction-arrested cells. In contracting cultures, NE induced a decrease of SERCA2 protein and mRNA levels by 40 and 60%, respectively. In contrast, SERCA2 protein and mRNA levels were not decreased by NE in contraction-arrested cells, indicating that contractility is a prerequisite for the negative influence of NE on SERCA2 expression. Electrical stimulation at a fixed frequency in the presence and absence of NE demonstrated that the NE-induced increase in contraction frequency is unlikely to account for the decreased SERCA2 expression induced by NE. The results suggest that the effect of contractility on SERCA2 expression depends on the signal transduction pathways that are activated by NE and T3.
心脏慢肌浆网Ca2+ -三磷酸腺苷酶（SERCA2）表达降低是Ca2+ 稳态的主要决定因素，它导致了衰竭心脏中细胞内Ca2+ 处理异常。我们研究了在无血清条件下，去甲肾上腺素（NE）和甲状腺激素（T3）对培养的新生心脏细胞中SERCA2表达影响的收缩性依赖性。NE和T3分别与病理性和生理性肥大形式相关，而这两种激素都会增加收缩性。在收缩的培养物中，T3使SERCA2蛋白和mRNA水平分别增加了35%和110%。在收缩停止的细胞中也发现了T3对SERCA2表达的相同刺激作用。在收缩的培养物中，NE使SERCA2蛋白和mRNA水平分别降低了40%和60%。相比之下，在收缩停止的细胞中，NE并没有降低SERCA2蛋白和mRNA水平，这表明收缩性是NE对SERCA2表达产生负面影响的先决条件。在有和没有NE的情况下以固定频率进行电刺激表明，NE诱导的收缩频率增加不太可能解释NE诱导的SERCA2表达降低。结果表明，收缩性对SERCA2表达的影响取决于由NE和T3激活的信号转导途径。
