Hydrogen peroxide alters splicing of soluble guanylyl cyclase and selectively modulates expression of splicing regulators in human cancer cells.
Hydrogen peroxide alters splicing of soluble guanylyl cyclase and selectively modulates expression of splicing regulators in human cancer cells.
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DOI：
10.1371/journal.pone.0041099
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Sharina IG
中科院分区：
文献类型：
--
作者：
Cote GJ;Zhu W;Thomas A;Martin E;Murad F;Sharina IG
可溶性鸟苷酸环化酶（sGC）在心血管、神经和胃肠道系统中一氧化氮（NO）介导的信号转导中起核心作用。选择性RNA剪接已成为调节sGC表达和活性的潜在机制。C-α 1 sGC是一种选择性剪接形式，对氧化诱导的蛋白质降解具有抗性，并表现出对内质网（ER）氧化环境的优先亚细胞分布。在此我们报道了在BE 2神经母细胞瘤和MDA-MD-468腺癌细胞中，H2O2处理可以调节C-α 1 sGC的剪接。此外，我们发现H2O2处理MDA-MD-468细胞选择性降低PTBP 1和hnRNP A2/B1剪接因子的蛋白水平，这些因子通过计算机分析被鉴定为潜在的α 1基因剪接调节因子。我们进一步证明，下调PTBP1的H2O2发生在蛋白质水平上，在不同的乳腺癌细胞中观察到可变的调节。我们的数据表明，H2O2调节RNA剪接，诱导抗氧化C-α 1 sGC亚基的表达。我们还报告说，H2O2治疗选择性地改变关键剪接调节剂的表达。这一过程可能在调节细胞对氧化应激条件的适应中发挥重要作用。
Soluble guanylyl cyclase (sGC) plays a central role in nitric oxide (NO)-mediated signal transduction in the cardiovascular, nervous and gastrointestinal systems. Alternative RNA splicing has emerged as a potential mechanism to modulate sGC expression and activity. C-α1 sGC is an alternative splice form that is resistant to oxidation-induced protein degradation and demonstrates preferential subcellular distribution to the oxidized environment of endoplasmic reticulum (ER). Here we report that splicing of C-α1 sGC can be modulated by H2O2 treatment in BE2 neuroblastoma and MDA-MD-468 adenocarcinoma human cells. In addition, we show that the H2O2 treatment of MDA-MD-468 cells selectively decreases protein levels of PTBP1 and hnRNP A2/B1 splice factors identified as potential α1 gene splicing regulators by in silico analysis. We further demonstrate that down-regulation of PTBP1 by H2O2 occurs at the protein level with variable regulation observed in different breast cancer cells. Our data demonstrate that H2O2 regulates RNA splicing to induce expression of the oxidation-resistant C-α1 sGC subunit. We also report that H2O2 treatment selectively alters the expression of key splicing regulators. This process might play an important role in regulation of cellular adaptation to conditions of oxidative stress.
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影响因子：
14.9
作者：
Desmet FO;Hamroun D;Lalande M;Collod-Béroud G;Claustres M;Béroud C
通讯作者：
Béroud C
影响因子：
5.3
作者：
Galban, Stefanie;Kuwano, Yuki;Gorospe, Myriam
通讯作者：
Gorospe, Myriam
影响因子：
158.5
作者：
Murad, Ferid
通讯作者：
Murad, Ferid
一氧化氮敏感的鸟类环酶α₁的氨基末端不影响二聚化，而会影响亚细胞定位。
影响因子：
3.7
作者：
Kraehling JR;Busker M;Haase T;Haase N;Koglin M;Linnenbaum M;Behrends S
通讯作者：
Behrends S
影响因子：
4.4
作者：
Koscielny, Gautier;Le Texier, Vincent;Gautheret, Daniel
通讯作者：
Gautheret, Daniel