Age increases expression and receptor-mediated activation of G alpha i in human atria.
Age increases expression and receptor-mediated activation of G alpha i in human atria.
复制标题
年龄增加了人类心房中 G α i 的表达和受体介导的激活。
DOI：
10.1097/00005344-200311000-00013
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发表时间：
2003
影响因子：
3
通讯作者：
Kwatra,MadanM
中科院分区：
文献类型：
--
作者：
Kilts,JasonD;Akazawa,Toshimasa;El-Moalem,HabibE;Mathew,JosephP;Newman,MarkF;Kwatra,MadanM
最近，我们发现人心房中的β 2 AR和其他几种Gα s偶联受体也与Gα i偶联，G α i是一种抑制腺苷酸环化酶（AC）的G蛋白。本研究旨在确定年龄是否会增加人心房Gα i的表达，更具体地说，是否会导致受体介导的Gα i激活增加。右心耳取自14例成年（40-55岁）和14例老年（71-79岁）心脏手术患者。心房膜的免疫印迹显示，老年人心房的Gα i2比成熟成人心房高82±18%（P< 0.002）;百日咳毒素催化的ADP-核糖基化以及[32 P]叠氮苯胺基-GTP的光亲和标记证实了Gα i随年龄的增加。我们还发现，老年人心房中受体介导的Gα i激活更大，基础和受体介导的AC活动在老年人心房中均降低。这些AC活性的降低可以通过用百日咳毒素使Gα i失活来逆转，表明Gα i表达和活化的年龄依赖性增加具有功能后果。由于人心房中的β 2 AR通过cAMP介导的受磷蛋白磷酸化介导收缩性，我们得出结论，年龄诱导的Gα i增加可能在抑制老年人心房的心功能中起作用。
Recently, we demonstrated that β 2 AR and several other Gα s-coupled receptors in human atria also couple to Gα i, a G protein that inhibits adenylyl cyclase (AC). The present study was undertaken to determine whether age increases expression of Gα i in human atrium, and more specifically whether it results in an increase in receptor-mediated activation of Gα i. Right atrial appendages were obtained from 14 mature adult (40–55 years) and 14 elderly (71–79 years) patients undergoing cardiac surgery. Immunoblotting of atrial membranes indicates that elderly atria have 82±18% more Gα i2 than atria from mature adults (P< 0.002); this increase in Gα i with age is confirmed by pertussis toxin-catalyzed ADP-ribosylation as well as by photoaffinity labeling with [32 P] azidoanilido-GTP. We also find that receptor-mediated activation of Gα i is greater in elderly atria and that both basal and receptor-mediated AC activities decrease in elderly atria. These decreases in AC activity can be reversed by disabling Gα i with pertussis toxin, indicating that the age-dependent increases in Gα i expression and activation have functional consequences. Because β 2 ARs in human atria mediate contractility through cAMP-mediated phosphorylation of phospholamban, we conclude that an age-induced increase in Gα i may have a role in depressing cardiac function in aged human atria.