Nitric oxide affects ERK signaling through down-regulation of MAP kinase phosphatase levels during larval development of the ascidian Ciona intestinalis.

Nitric oxide affects ERK signaling through down-regulation of MAP kinase phosphatase levels during larval development of the ascidian Ciona intestinalis.
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DOI:
10.1371/journal.pone.0102907
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Palumbo A
Palumbo A
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Castellano I;Ercolesi E;Palumbo A

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在海鞘中,海鞘幼虫的发育和变态需要复杂的事件相互作用,包括一氧化氮(NO)的产生,MAP激酶(ERK,JNK)和caspase-3激活。我们以前已经表明,NO水平影响变态率,调节半胱天冬酶活性,促进氧化应激途径,导致蛋白质硝化。在这里,我们报告说,NO下调MAP激酶磷酸酶(mkps)的表达影响积极的ERK信号。通过药理学方法,我们观察到内源性NO水平的降低引起ERK磷酸化的减少,而NO水平的升高诱导ERK活化。通过定量基因表达分析,我们还确定了NO对ERK基因网络的影响,包括mpk 1、mpk 3和一些关键的发育基因。我们证明,NO诱导ERK独立下调mkp 1和mkp 3,负责维持ERK磷酸化水平的关键变态基因,如激素受体rev-erb和货车维勒布兰德蛋白vwa 1c的转录。这些结果为NO在玻璃海鞘幼虫发育和变态过程中所发挥的作用提供了新的见解,强调了不同信号通路之间的串扰。
In the ascidian Ciona intestinalis larval development and metamorphosis require a complex interplay of events, including nitric oxide (NO) production, MAP kinases (ERK, JNK) and caspase-3 activation. We have previously shown that NO levels affect the rate of metamorphosis, regulate caspase activity and promote an oxidative stress pathway, resulting in protein nitration. Here, we report that NO down-regulates MAP kinase phosphatases (mkps) expression affecting positively ERK signaling. By pharmacological approach, we observed that the reduction of endogenous NO levels caused a decrease of ERK phosphorylation, whereas increasing levels of NO induced ERK activation. We have also identified the ERK gene network affected by NO, including mpk1, mpk3 and some key developmental genes by quantitative gene expression analysis. We demonstrate that NO induces an ERK-independent down-regulation of mkp1 and mkp3, responsible for maintaining the ERK phosphorylation levels necessary for transcription of key metamorphic genes, such as the hormone receptor rev-erb and the van willebrand protein vwa1c. These results add new insights into the role played by NO during larval development and metamorphosis in Ciona, highlighting the cross-talk between different signaling pathways.
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