摘要
Reactive oxygen species （ROS） attack guanine bases in DNA easily and form 8-hydroxydeoxyguanosine （8-OHdG）, which can bind to thymidine rather than cytosine, based on which, the level of 8-OHdG is gen- erally regarded as a biomarker of mutagenesis conse- quent to oxidative stress. For example, higher levels of 8-OHdG are noted in Helicobacter pylori-associated chronic atrophic gastritis as well as gastric cancer. However, we have found that exogenous 8-OHdG can paradoxically reduce ROS production, attenuate the nuclear factor-KB signaling pathway, and ameliorate the expression of proinflammatory mediators such as interleukin （IL）-I, IL-6, cyclo-oxygenase-2, and induc- ible nitric oxide synthase in addition to expression of nicotinamide adenine dinucleotide phosphate oxidase （NOX）-I, NOX organizer-1 and NOX activator-1 in vari- ous conditions of inflammation-based gastrointestinal （GI） diseases including gastritis, inflammatory bowel disease, pancreatitis, and even colitis-associated carci- nogenesis. Our recent finding that exogenous 8-OHdG was very effective in either inflammation-based or oxidative-stress-associated diseases of stress-related mucosal damage has inspired the hope that synthetic 8-OHdG can be a potential candidate for the treatment of inflammation-based GI diseases, as well as the pre- vention of inflammation-associated GI cancer. In this editorial review, the novel fact that exogenous 8-OHdG can be a functional molecule regulating oxidative- stress-induced gastritis through either antagonizing Rac-guanosine triphosphate binding or blocking the signals responsible for gastric inflammatory cascade is introduced.
Reactive oxygen species (ROS) attack guanine bases in DNA easily and form 8-hydroxydeoxyguanosine (8-OHdG),which can bind to thymidine rather than cytosine,based on which,the level of 8-OHdG is gen-erally regarded as a biomarker of mutagenesis conse-quent to oxidative stress.For example,higher levels of 8-OHdG are noted in Helicobacter pylori-associated chronic atrophic gastritis as well as gastric cancer.However,we have found that exogenous 8-OHdG can paradoxically reduce ROS production,attenuate thenuclear factor-κB signaling pathway,and ameliorate the expression of proinflammatory mediators such as interleukin (IL)-1,IL-6,cyclo-oxygenase-2,and induc-ible nitric oxide synthase in addition to expression of nicotinamide adenine dinucleotide phosphate oxidase (NOX)-1,NOX organizer-1 and NOX activator-1 in vari-ous conditions of inflammation-based gastrointestinal (GI) diseases including gastritis,inflammatory bowel disease,pancreatitis,and even colitis-associated carci-nogenesis.Our recent finding that exogenous 8-OHdG was very effective in either inflammation-based or oxidative-stress-associated diseases of stress-related mucosal damage has inspired the hope that synthetic 8-OHdG can be a potential candidate for the treatment of inflammation-based GI diseases,as well as the pre-vention of inflammation-associated GI cancer.In this editorial review,the novel fact that exogenous 8-OHdG can be a functional molecule regulating oxidative-stress-induced gastritis through either antagonizing Rac-guanosine triphosphate binding or blocking the signals responsible for gastric inflammatory cascade is introduced.
基金
Supported by A grant from the Ministry of Education and Science Technology,South Korea,No.2010-0002052
