It is unknown whether base excision DNA repair (BER) proteins interact with mitogen-activated protein kinases (MAPK) under oxidation. Here, we explored roles of BER proteins in signaling transduction involving MAPK during hyperoxia. We demonstrated that ERK1/2 phosphorylation in A549 cells was increased in 95% O(2). p38 activity in A549 cells was also increased by exposure to 95% O(2). To evaluate regulatory roles of MAPK, we have transduced A549 cells and primary alveolar epithelial type II cells (AECII) to overexpress 8-oxoguanine DNA glycosylase (hOgg1). Overexpression of hOgg1 reduced hyperoxic toxicity in A549 and AECII cells. Furthermore, protection by BER against hyperoxia appeared to involve an upregulation of ERK1/2 and downregulation of p38. These observations demonstrate, for the first time, that reduction of hyperoxic toxicity by BER proteins may be involved with MAPK activity, thereby impacting cell survival. Furthermore, our studies suggest that modulation of MAPK may be used in combination with BER proteins to counteract hyperoxic toxicity.

中文翻译：

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人8-氧鸟嘌呤DNA糖基化酶增加了对肺上皮细胞高氧细胞毒性的抵抗力，并参与了MAPK活性的改变。

尚不清楚碱基切除DNA修复（BER）蛋白是否在氧化作用下与丝裂原激活的蛋白激酶（MAPK）相互作用。在这里，我们探讨了高氧时BER蛋白在涉及MAPK的信号转导中的作用。我们证明，在A549细胞中ERK1 / 2磷酸化在95％O（2）中增加。通过暴露于95％O（2），A549细胞中的p38活性也增加了。为了评估MAPK的调节作用，我们已经转导了A549细胞和II型初级肺泡上皮细胞（AECII），以过表达8-氧鸟嘌呤DNA糖基化酶（hOgg1）。hOgg1的过表达降低了A549和AECII细胞的高氧毒性。此外，BER对高氧的保护似乎涉及ERK1 / 2的上调和p38的下调。这些观察结果首次证明，BER蛋白降低高氧毒性可能与MAPK活性有关，从而影响细胞存活。此外，我们的研究表明，MAPK的调节可与BER蛋白结合使用以抵消高氧毒性。