G alpha(q)-coupled receptors in human atrium function through protein kinase C epsilon and delta.
G alpha(q)-coupled receptors in human atrium function through protein kinase C epsilon and delta.
复制标题
人心房中的 G α(q) 偶联受体通过蛋白激酶 C epsilon 和 delta 发挥作用。
DOI：
10.1016/j.yjmcc.2004.11.011
复制
发表时间：
2005
影响因子：
5
通讯作者：
Kwatra,MadanM
中科院分区：
文献类型：
--
作者：
Kilts,JasonD;Grocott,HilaryP;Kwatra,MadanM
心脏GαQ偶联受体(如内皮素、血管紧张素和α1肾上腺素能受体)介导心脏变力和变时性，以及肥厚的发展。这些受体通过蛋白激酶C(PKC)来传递信号，PKC是一个由12个同工酶组成的家族，包括PKCα，βI、βII、γ，δ，ε，θ，η，λ，ι，ζ和μ。在这些同工酶中，α，βII、γ，ε，δ和ζ在不同的动物模型中通过心脏GαQ偶联受体参与信号传导。然而，特定的G-αQ偶联受体激活哪些同工酶的图谱在不同的动物物种中是不同的。因此，这些结果不能外推到人的心脏。在这项研究中，我们检测了三种不同的G-αQ偶联受体激活的人心房组织中的蛋白激酶C同工酶。用G-αQ偶联受体激动剂处理活体心耳，免疫印迹法检测细胞内蛋白激酶C同工酶的再分布。我们发现，在急性(5min)和长时间(35min)刺激下，刺激人心房GαQ偶联受体只激活PKCε和δ。此外，PKCε和δ显示出不同的亚细胞再分布模式；在Gαq刺激下，两者都转移到质膜上，PKCδ也重新分布到线粒体。结论：PKC、ε和δ是参与人心房GαQ信号转导的主要同工酶。
Cardiac Gαq-coupled receptors (such as endothelin, angiotensin, and α1-adrenergic receptors) mediate cardiac inotropy and chronotropy, as well as the development of hypertrophy. These receptors signal through protein kinase C (PKC), a family of 12 isozymes including PKC α, βI, βII, γ, δ, ε, θ, η, λ, ι, ζ, and μ. Of these PKC isozymes, α, βII, γ, ε, δ, and ζ have been implicated in signaling through cardiac Gαq-coupled receptors in various animal models. However, the profile of which isozymes are activated by a given Gαq-coupled receptor varies among animal species. Thus, these results can not be extrapolated to human heart. In this study, we examine PKC isozymes activated by three different Gαq-coupled receptors in human atrial tissue. Live atrial appendages obtained from the operating room were sliced and treated with agonists of Gαq-coupled receptors, and cellular redistribution of PKC isozymes was examined by immunoblotting. We find that stimulation of Gαq-coupled receptors in human atrium activates PKC ε and δ only, under both acute (5 min) and longer (35 min) stimulations. Further, PKC ε and δ exhibit distinct subcellular redistribution patterns; while both translocate to the plasma membrane upon Gαqstimulation, PKC δ also redistributes to mitochondria. We conclude that PKC ε and δ are the main PKC isozymes involved in Gαq-mediated signaling in human atria.