위장상피세포에서 헬리코박터 파이로리에 의한 오토파지 유도에 있어서 Nrf2의 역할

Abstract

It has been reported that Helicobacter pylori (H. pylori) infection is one of the primary causes of gastritis and peptic ulcer diseases, which are provoked by oxidative stress and inflammation. More than 50% of the worlds population is supposed to be infected by this bacterium. However, 90% of infected patients are asymptomatic, indicative of the existence of host defense mechanisms. Among them, nuclear factor-erythroid 2p45 (NF-E2)-related factor (Nrf2) is speculated to be involved in cellular defence against the H. pylori-induced gastritis. 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 response to H. pylori-induced gastric inflammation, human gastric cancer cells (AGS cells) were infected with H. pylori. In this study, I found that H. pylori infection induces up-regulation of microtubule-associated light chain3 (LC3), an autophagic marker, by inducing accumulation of reactive oxygen species (ROS) and subsequently nuclear translocalization of Nrf2 in AGS cells. Notably, p62/SQSTM1, one of well-known autophagic substrates, regulated Nrf2 activation by H. pylori. Furthermore, Nrf2-induced LC3 up-regulation was mediated by heme oxygenase-1 and the generation of its by-product, carbon monoxide. H. pylori infection induced Nrf2 activation and p62 accumulation in C57BL6 female mice as well. Taken together, Nrf2 is considered to play a role in cellular adaptive response to H. pylori-induced gastritis by inducing autophagy.