Circadian profiles in the embryonic chick heart: L-type voltage-gated calcium channels and signaling pathways.
Circadian profiles in the embryonic chick heart: L-type voltage-gated calcium channels and signaling pathways.
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DOI：
10.3109/07420528.2010.514631
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发表时间：
2010-10
影响因子：
2.8
通讯作者：
Ko GY
中科院分区：
文献类型：
--
作者：
Ko ML;Shi L;Grushin K;Nigussie F;Ko GY
生物钟存在于心脏组织中，调节多种生理事件，从心脏代谢到收缩功能，以及昼夜节律振荡器和代谢相关基因的表达。大量证据表明，成年哺乳动物心肌细胞存在内源性昼夜节律振荡器。然而，哺乳动物胚胎不可能在没有母体影响的情况下独立进入体内的光-暗(LD)周期，但昼夜节律基因在胚胎阶段得到很好的表达并能够振荡。作者利用独立于母体影响的鸡胚胎来研究胚胎心脏是否可以在卵子的LD周期下携带。作者发现了L型电压门控钙通道(L-VGCCs)的昼夜节律，这种离子通道负责鸡胚胎心脏产生心肌收缩。VGCCα1C和VGCCα1D的基因水平和蛋白表达均受昼夜节律控制，夜间记录心肌细胞时，VGCC-VGCC的平均电流密度明显大于白天。细胞外信号调节蛋白(ERK)、应激激活蛋白激酶(P38)、蛋白激酶B(AKT)和糖原合成酶β(GSK-3β)等参与胰岛素信号转导和心脏代谢的几种蛋白的磷酸化状态也受到昼夜节律的控制。ERK和p38都参与了心肌收缩能力的调节和各种病理状态的发生，如心肌肥厚和心力衰竭。尽管ERK和PI3K-Akt信号通路都参与了有关心肌细胞生理或病理状态的复杂细胞过程，但心脏中的昼夜节律振荡器独立地调节这些通路，这两条信号通路都参与了L-VGCC的昼夜节律调节。
Circadian clocks exist in the heart tissue and modulate multiple physiological events, from cardiac metabolism to contractile function and expression of circadian oscillator and metabolic-related genes. Ample evidence has demonstrated that there are endogenous circadian oscillators in adult mammalian cardiomyocytes. However, mammalian embryos cannot be entrained independently to light-dark (LD) cycles in vivo without any maternal influence, but circadian genes are well expressed and able to oscillate in embryonic stages. The authors took advantage of using chick embryos that are independent of maternal influences to investigate whether embryonic hearts could be entrained under LD cycles in ovo. The authors found circadian regulation of L-type voltage-gated calcium channels (L-VGCCs), the ion channels responsible for the production of cardiac muscle contraction in embryonic chick hearts. The mRNA levels and protein expression of VGCCα1C and VGCCα1D are under circadian control, and the average L-VGCC current density is significantly larger when cardiomyocytes are recorded during the night than day. The phosphorylation states of several kinases involved in insulin signaling and cardiac metabolism, including extracellular signal-regulated kinase (Erk), stress-activated protein kinase (p38), protein kinase B (Akt), and glycogen synthase kinase-3β (GSK-3β), are also under circadian control. Both Erk and p38 have been implicated in regulating cardiac contractility and in the development of various pathological states, such as cardiac hypertrophy and heart failure. Even though both Erk and phosphoinositide 3-kinase (PI3K)-Akt signaling pathways participate in complex cellular processes regarding physiological or pathological states of cardiomyocytes, the circadian oscillators in the heart regulate these pathways independently, and both pathways contribute to the circadian regulation of L-VGCCs.
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影响因子：
5.5
作者：
Gaborit, Nathalie;Le Bouter, Sabrina;Demolombe, Sophie
通讯作者：
Demolombe, Sophie
影响因子：
2.5
作者：
Butcher, GQ;Lee, BY;Obrietan, K
通讯作者：
Obrietan, K
影响因子：
20.1
作者：
Durgan DJ;Pulinilkunnil T;Villegas-Montoya C;Garvey ME;Frangogiannis NG;Michael LH;Chow CW;Dyck JR;Young ME
通讯作者：
Young ME
DOI：
10.1152/ajpheart.01344.2005
发表时间：
2006-06-01
影响因子：
4.8
作者：
Durgan, David J.;Smith, Justin K.;Young, Martin E.
通讯作者：
Young, Martin E.
影响因子：
4.5
作者：
Fan, JS;Palade, P
通讯作者：
Palade, P