ERK1/2-mediated phosphorylation of myometrial caldesmon during pregnancy and labor
ERK1/2-mediated phosphorylation of myometrial caldesmon during pregnancy and labor
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DOI：
10.1152/ajpregu.00290.2002
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发表时间：
2003-01-01
影响因子：
2.8
通讯作者：
Morgan, KG
中科院分区：
文献类型：
--
作者：
Li, YP;Je, HD;Morgan, KG
我们使用了一个定时怀孕的大鼠模型来追踪妊娠和分娩期间子宫肌收缩力的变化，并将这些变化与上游信号事件联系起来。从co2安乐死的大鼠身上采集子宫肌层。妊娠第16天和第20天，宫缩幅度有所增加，但宫缩发生率和宫缩力曲线下面积受到抑制，与妊娠期肌层静止一致。Ca2+对收缩的敏感性在怀孕20天时下降，在分娩时部分逆转。h-caldesmon （h-CaD）蛋白含量在妊娠期升高。在分娩过程中，ERK1/2位点特异性磷酸化的phospho-CaD抗体的信号增加了40倍。ERK1/2的激活在分娩开始时显著增加。肌球蛋白轻链磷酸化（LC20-P）在产程与非妊娠状态相比显著升高。因此，我们得出结论，妊娠期间CaD蛋白含量的增加可能有助于抑制妊娠肌层的收缩性。相反，CaD磷酸化，通过erk1 /2介导的信号通路，以及基础LC20-P的增加，被认为有助于逆转抑制并促进分娩期间子宫收缩。
We used a timed-pregnant rat model to track changes in myometrial contractility during pregnancy and labor and to correlate these changes with upstream signaling events. Myometrium was harvested from CO2-euthanized rats. Although contraction amplitudes increased at 16 and 20 days of pregnancy, contraction incidence and area under the force curve were inhibited, consistent with the myometrial quiescence of pregnancy. The Ca2+ sensitivity of contraction was decreased at 20 days of pregnancy and this was partially reversed in labor. The protein content of h-caldesmon (h-CaD) was increased in pregnancy. A 40-fold increase in the signal from a phospho-CaD antibody specific for phosphorylation at an ERK1/2 site occurred during labor. ERK1/2 activation increased significantly at the onset of labor. Myosin light chain phosphorylation (LC20-P) increased significantly in labor compared with the nonpregnant state. Thus we conclude that the increase in CaD protein content during pregnancy may contribute to a suppression of the contractility of pregnant myometrium. Conversely, CaD phosphorylation, through an ERK1/2-mediated signaling pathway, as well as an increase in basal LC20-P, is suggested to contribute to the reversal of inhibition and promote contraction of the uterus during labor.