Institute of Virology, Department of Medical Microbiology and Hygiene, University Medical Center, Freiburg D-79104, Germany, Institute of Medical Microbiology, Charité, Berlin D-12203, Germany and Institute of Immunology and Institute of Microbiology, Department of Medical Microbiology and Hygiene, University Medical Center, Freiburg D-79104, Germany
Institute of Medical Microbiology, Charité, Berlin D-12203, Germany and.
Carcinogenesis. 2014 Jul;35(7):1582-91. doi: 10.1093/carcin/bgu074. Epub 2014 Mar 24.
Malignant transformation of gastric epithelial cells by chronic Helicobacter pylori infection is caused by several mechanisms including attraction of reactive oxygen species (ROS)-producing neutrophils and cytotoxin-associated antigen A-mediated dysplastic alterations. Here we show that H.pylori protects transformed cells from ROS-mediated intercellular induction of apoptosis. This potential control step in oncogenesis depends on the HOCl and NO/peroxynitrite (PON) signaling pathways. Helicobacter pylori-associated catalase and superoxide dismutase (SOD) efficiently cooperate in the inhibition of HOCl and the NO/PON signaling pathways. Helicobacter pylori catalase prevents HOCl synthesis through decomposition of hydrogen peroxide. Helicobacter pylori-associated SOD interferes with the crucial interactions between superoxide anions and HOCl, as well as superoxide anions and NO. The ratio of bacteria to malignant cells is critical for sufficient protection of transformed cells. Low concentrations of H.pylori more efficiently inhibited ROS-mediated destruction of transformed cells when compared with high concentrations of bacteria. Our data demonstrate the critical role of H.pylori antioxidant enzymes in the survival of transformed cells, modulating an early step of oncogenesis that is distinct from the transformation process per se.
慢性幽门螺杆菌感染导致胃上皮细胞恶性转化，其机制包括吸引产生活性氧（ROS）的中性粒细胞和细胞毒素相关抗原 A 介导的发育异常改变。在这里，我们表明幽门螺杆菌可以保护转化细胞免受 ROS 介导的细胞间凋亡诱导。这一潜在的致癌控制步骤依赖于次氯酸（HOCl）和一氧化氮/过氧亚硝酸盐（PON）信号通路。幽门螺杆菌相关的过氧化氢酶和超氧化物歧化酶（SOD）在抑制 HOCl 和 NO/PON 信号通路方面高效合作。幽门螺杆菌过氧化氢酶通过分解过氧化氢来防止 HOCl 的合成。幽门螺杆菌相关的 SOD 干扰超氧阴离子和 HOCl 以及超氧阴离子和 NO 之间的关键相互作用。细菌与恶性细胞的比例对于转化细胞的充分保护至关重要。与高浓度细菌相比，低浓度的幽门螺杆菌更有效地抑制 ROS 介导的转化细胞破坏。我们的数据表明，幽门螺杆菌抗氧化酶在转化细胞的存活中起着关键作用，调节了致癌作用的早期步骤，这与转化过程本身不同。
