Katayama Yasumi, Takahashi Morio, Kuwayama Hajime
Department of Gastroenterology and Hepatology, Dokkyo Medical University, Koshigaya Hospital, Saitama, Japan.
Biochem Biophys Res Commun. 2009 Oct 23;388(3):496-500. doi: 10.1016/j.bbrc.2009.08.003. Epub 2009 Aug 5.
Previous reports have indicated that Helicobacter pylori (H. pylori) causes epigenetic changes of certain genes such as cancer suppression genes, which may be associated with carcinogenesis. However, the mechanism by which it causes epigenetic changes in certain genes and not in others is unclear. Presently, we focused on a cancer suppression gene, runx3, and demonstrated the following: (1) H. pylori induces nitric oxide (NO) production in macrophages. (2) NO causes methylation of runx3 in epithelial cells. (3) H. pylori induces the methylation of epithelial cells in the presence of macrophages, which is reversed by an NO-specific inhibitor. These results indicate that H. pylori-induced methylation is mediated by NO, and suggest that NO may be a key to the mechanism of how H. pylori causes epigenetic changes in certain genes. Additionally, we demonstrated that lipopolysaccharide, as well as H. pylori, induces NO-mediated methylation, indicating that other inflammation inducers beside H. pylori might induce aberrant methylation of runx3.
先前的报告表明，幽门螺杆菌（H. pylori）会导致某些基因发生表观遗传变化，如抑癌基因，这可能与致癌作用有关。然而，其导致某些基因而非其他基因发生表观遗传变化的机制尚不清楚。目前，我们聚焦于一个抑癌基因runx3，并证明了以下几点：（1）幽门螺杆菌可诱导巨噬细胞产生一氧化氮（NO）。（2）NO导致上皮细胞中runx3发生甲基化。（3）幽门螺杆菌在巨噬细胞存在的情况下诱导上皮细胞甲基化，而这种甲基化可被NO特异性抑制剂逆转。这些结果表明，幽门螺杆菌诱导的甲基化是由NO介导的，这表明NO可能是幽门螺杆菌导致某些基因发生表观遗传变化机制的关键。此外，我们证明脂多糖以及幽门螺杆菌均可诱导NO介导的甲基化，这表明除幽门螺杆菌外的其他炎症诱导剂可能会诱导runx3发生异常甲基化。
