Adenylyl cyclase type 5 protein expression during cardiac development and stress
Adenylyl cyclase type 5 protein expression during cardiac development and stress
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DOI：
10.1152/ajpheart.00050.2009
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发表时间：
2009-11-01
影响因子：
4.8
通讯作者：
Vatner, Dorothy E.
中科院分区：
文献类型：
--
作者：
Hu, Che-Lin;Chandra, Rachna;Vatner, Dorothy E.
胡C，钱德拉R，葛H，疼痛J，严L，巴布G，抑郁C，岩坪K，石川Y，佐渡岛J，Vatner SF，Vatner DE。腺苷酸环化酶5蛋白在心脏发育和应激中的表达。Am J Physiol Heart Circ Physiol 297：H1776-H1782，2009.首次发表于2009年9月4日; doi：10.1152/ajpheart.00050.2009。腺苷酸环化酶（AC）5型和6型（AC 5和AC 6）是哺乳动物心脏中表达的两种主要AC亚型，介导来自β-肾上腺素能受体刺激的信号。由于缺乏同种型特异性抗体，很难确定心脏中AC 5蛋白的表达水平。在这里，我们证明了成功产生的AC 5亚型特异性小鼠单克隆抗体，并研究了AC 5蛋白在不同哺乳动物物种的心脏发育过程中的表达。使用来自AC 5敲除小鼠和来自过表达AC 5的转基因小鼠的心脏和脑组织证实了抗体的特异性。在小鼠中，AC 5蛋白在脑中含量最高，但在所有研究器官中也可检测到，包括心脏、脑、肺、肝、胃、肾、骨骼肌和血管组织。蛋白质印迹分析表明，AC 5是最丰富的新生儿心脏和下降到基础水平，在成人心脏。AC 5蛋白在压力超负荷性左室肥厚心脏中增加。因此，这种新的AC 5抗体证明这种AC同种型的行为类似于胎儿型基因，例如心房利钠肽;即，它随发育而下降，随压力超负荷肥大而增加。
Hu C, Chandra R, Ge H, Pain J, Yan L, Babu G, Depre C, Iwatsubo K, Ishikawa Y, Sadoshima J, Vatner SF, Vatner DE. Adenylyl cyclase type 5 protein expression during cardiac development and stress. Am J Physiol Heart Circ Physiol 297: H1776-H1782, 2009. First published September 4, 2009; doi:10.1152/ajpheart.00050.2009.-Adenylyl cyclase (AC) types 5 and 6 (AC5 and AC6) are the two major AC isoforms expressed in the mammalian heart that mediate signals from beta-adrenergic receptor stimulation. Because of the unavailability of isoform-specific antibodies, it is difficult to ascertain the expression levels of AC5 protein in the heart. Here we demonstrated the successful generation of an AC5 isoform-specific mouse monoclonal antibody and studied the expression of AC5 protein during cardiac development in different mammalian species. The specificity of the antibody was confirmed using heart and brain tissues from AC5 knockout mice and from transgenic mice overexpressing AC5. In mice, the AC5 protein was highest in the brain but was also detectable in all organs studied, including the heart, brain, lung, liver, stomach, kidney, skeletal muscle, and vascular tissues. Western blot analysis showed that AC5 was most abundant in the neonatal heart and declined to basal levels in the adult heart. AC5 protein increased in the heart with pressure-overload left ventricular hypertrophy. Thus this new AC5 antibody demonstrated that this AC isoform behaves similarly to fetal type genes, such as atrial natriuretic peptide; i.e., it declines with development and increases with pressureoverload hypertrophy.