Key Laboratory of Ion Beam Bioengineering, Chinese Academy of Science, Hefei, 230031, People's Republic of China.
J Biochem Mol Toxicol. 2013 Jun;27(6):323-9. doi: 10.1002/jbt.21491. Epub 2013 May 6.
Detoxification enzyme heme oxygenase 1 (HO-1) and proinflammation enzyme cyclooxygenase 2 (Cox-2) are key response proteins that function to promote the survival of cells exposed to arsenic trioxide (ATO). However, whether there is a cross-regulation between them in ATO-treated cells remains poorly investigated. In this study, concomitant upregulation of Cox-2 and HO-1 induced by ATO was observed in normal human lung fibroblasts. Cox-2 inhibitor NS398 suppressed the upregulation of HO-1, whereas HO-1 inhibitor protoporphyrin IX zinc (II) stimulated the expression of Cox-2. Both proteins were regulated by p38, and the feedback regulation of HO-1 on Cox-2 was mediated through p38. Our results confirmed the reciprocal regulations between Cox-2 and HO-1 in ATO-treated normal cells and shed light on the understanding of protecting cells from injury caused by ATO while simultaneously decreasing the inflammation responses, which may be related to the carcinogenicity of ATO.
解毒酶血红素加氧酶 1（HO-1）和促炎酶环氧化酶 2（Cox-2）是功能上促进暴露于三氧化二砷（ATO）的细胞存活的关键反应蛋白。然而，ATO 处理的细胞中它们之间是否存在交叉调节仍研究甚少。在这项研究中，在正常的人肺成纤维细胞中观察到 ATO 诱导的 Cox-2 和 HO-1 的同时上调。Cox-2 抑制剂 NS398 抑制了 HO-1 的上调，而 HO-1 抑制剂原卟啉 IX 锌（II）则刺激了 Cox-2 的表达。这两种蛋白都受到 p38 的调节，HO-1 对 Cox-2 的反馈调节是通过 p38 介导的。我们的研究结果证实了 Cox-2 和 HO-1 在 ATO 处理的正常细胞之间的相互调节，并阐明了在同时减少炎症反应的情况下保护细胞免受 ATO 损伤的机制，这可能与 ATO 的致癌性有关。
