Tumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul National University, Seoul 08826, South Korea.
Tumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul National University, Seoul 08826, South Korea; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Sciences and Technology, Seoul National University, Seoul 08826, South Korea.
Biochem Pharmacol. 2019 Apr;162:89-97. doi: 10.1016/j.bcp.2019.02.003. Epub 2019 Feb 4.
It has been reported that Helicobacter pylori (H. pylori) infection is one of the primary causes of gastritis and peptic ulcer diseases. More than 50% of the world's population is supposed to be infected by this bacterium. However, 90% of infected patients do not develop gastric cancer, suggesting the existence of host defence mechanisms. Nrf2 is a transcription factor that plays a key role in cellular defence against oxidative stress and inflammation. Autophagy, an autodigestive process that degrades cellular organelles and proteins, plays an important role in maintaining cellular homeostasis. To investigate the molecular mechanisms responsible for cellular adaptive response to H. pylori induced gastric inflammation, human gastric epithelial cells and mice were infected with H. pylori. H. pylori infection induced expression of microtubule-associated light chain3 (LC3), an autophagic marker, through accumulation of reactive oxygen species and subsequently nuclear translocation of the redox-sensitive transcription factor, Nrf2 in human gastric epithelial AGS cells. Furthermore, Nrf2-induced LC3 up-regulation was mediated by heme oxygenase-1 (HO-1) and its by-product, carbon monoxide. Taken together, the Nrf2-HO-1 axis is considered to play a role in cellular adaptive survival response to H. pylori-induced gactric carcinogenesis by inducing autophagy.
据报道，幽门螺杆菌（H. pylori）感染是胃炎和消化性溃疡病的主要病因之一。世界上超过 50%的人口被认为感染了这种细菌。然而，90%的感染患者不会发展为胃癌，这表明宿主存在防御机制。Nrf2 是一种转录因子，在细胞对氧化应激和炎症的防御中起着关键作用。自噬是一种降解细胞细胞器和蛋白质的自噬过程，在维持细胞内稳态方面起着重要作用。为了研究细胞对 H. pylori 诱导的胃炎症适应性反应的分子机制，用人胃上皮细胞和小鼠进行了 H. pylori 感染实验。H. pylori 感染通过积累活性氧诱导微管相关轻链 3（LC3），一种自噬标志物，随后核易位到氧化还原敏感转录因子 Nrf2，在人胃上皮细胞 AGS 中。此外，Nrf2 诱导的 LC3 上调是由血红素加氧酶-1（HO-1）及其产物一氧化碳介导的。总之，Nrf2-HO-1 轴被认为通过诱导自噬在细胞对 H. pylori 诱导的胃致癌作用的适应性存活反应中发挥作用。
