Endothelin-1 induced hypertrophic effect in neonatal rat cardiomyocytes:: Involvement of Na+/H+ and Na+/Ca2+ exchangers
Endothelin-1 induced hypertrophic effect in neonatal rat cardiomyocytes:: Involvement of Na+/H+ and Na+/Ca2+ exchangers
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DOI：
10.1016/j.yjmcc.2006.05.016
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发表时间：
2006-11-01
影响因子：
5
通讯作者：
Camilion de Hurtado, Maria C.
中科院分区：
文献类型：
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作者：
Dulce, Raul A.;Hurtado, Cecilia;Camilion de Hurtado, Maria C.
Endothelin-1 (ET-1) 是一种有效的细胞生长激动剂，还可刺激 Na+/H+ 交换异构体 1 (NHE-1) 活性。据推测，NHE-1 活性介导的细胞内 Na+ ([Na+](i)) 增加可能会诱导 Na+/Ca2+ 交换器 (NCXrev) 的反向模式增加细胞内 Ca2+ ([Ca2+](i))，进而诱导肥大。这项工作的目的是测试 NHE-1 或 NCXrev 的抑制是否可以预防 ET-1 诱导的新生大鼠心肌细胞 (NRVM) 肥大。 NRVM 在不存在（对照）和单独存在 5 nmol/L ET-1 或与 1 μmol/L HOE 642 或 5 μmol/L KB-R7943 组合的情况下培养（24 小时）。 ET-1 使细胞表面积、H-3-苯丙氨酸掺入和心房钠尿因子 (ANF) mRNA 表达分别增加至对照的 131 +/- 3、220 +/- 12 和 190 +/- 25%（P < 0.05）。 ET-1 处理的 [Na+](i) 和总 [Ca2+](i) 较高（分别为 8.1 +/- 1.2 mmol/L 和 636 +/- 117 nmol/L），而对照 NRVM 则高于对照 NRVM（分别为 4.2 +/- 1.3 和 346 +/- 85，P < 0.05），HOE 642 抑制 NHE-1 抵消了这种影响。 ET-1 处理组中细胞外 Na+ 去除 (NCXrev) 诱导的 [Ca2+]i 含量高于对照 NRVM，并且通过与 HOE 642 或 KB-R7943（NCXrev 抑制剂）共同处理可防止该效应。 ET-1 诱导的细胞面积增加、ANF mRNA 表达和 ET-1 处理的 NRVM 中的 H-3-苯丙氨酸掺入因 NHE-1 或 NCXrev 抑制而减少。我们的结果提供了第一个证据，表明 NCXrev 除了 NHE-1 激活之外，还参与 ET-1 诱导的 NRVM 肥大。 (c) 2006 年，爱思唯尔公司出版。
Endothelin-1 (ET-1) is a potent agonist of cell growth that also stimulates Na+/H+ exchanger isoform 1 (NHE-1) activity. It was hypothesized that the increase in intracellular Na+ ([Na+](i)) mediated by NHE-1 activity may induce the reverse mode of Na+/Ca2+ exchanger (NCXrev) increasing intracellular Ca2+ ([Ca2+](i)) which in turn will induce hypertrophy. The objective of this work was to test whether the inhibition of NHE-1 or NCXrev prevents ET-1 induced hypearophy in neonatal rat cardiomyocytes (NRVMs). NRVMs were cultured (24 h) in the absence (control) and presence of 5 nmol/L ET-1 alone, or combined with 1 mu mol/L HOE 642 or 5 mu mol/L KB-R7943. Cell surface area, H-3-phenylalanine incorporation and atrial natriuretic factor (ANF) mRNA expression were increased to 131 +/- 3, 220 +/- 12 and 190 +/- 25% of control, respectively (P < 0.05) by ET-1. [Na+](i) and total [Ca2+](i) were higher (8.1 +/- 1.2 mmol/L and 636 +/- 117 nmol/L, respectively) in ET-1-treated than in control NRVMs (4.2 +/- 1.3 and 346 +/- 85, respectively, P < 0.05), effects that were cancelled by NHE-1 inhibition with HOE 642. The rise in [Ca2+]i induced by extracellular Na+ removal (NCXrev) was higher in ET-1-treated than in control NRVMs and the effect was prevented by co-treatment with HOE 642 or KB-R7943 (NCXrev inhibitor). The ET-1-induced increase in cell area, ANF mRNA expression and H-3-phenytalanine incorporation in ET-1-treated NRVM were decreased by NHE-1 or NCXrev inhibition. Our results provide the first evidence that NCXrev is, secondarily to NHE-1 activation, involved in ET-1-induced hypertrophy in NRVMs. (c) 2006 Published by Elsevier Inc.