Abstract
Helicobacter pylori (H. pylori) causes gastritis and gastric cancers. Oxidative stress is involved in the pathological mechanism of H. pylori-induced gastritis and gastric cancer induction. Therefore, reducing oxidative stress may be beneficial for preventing the development of H. pylori-associated gastric diseases. Nuclear factor erythroid-2-related factor 2 (Nrf2) is a crucial regulator for the expression of antioxidant enzyme heme oxygenase-1 (HO-1), which protects cells from oxidative injury. α-Lipoic acid (α-LA), a naturally occurring dithiol, shows antioxidant and anti-inflammatory effects in various cells. In the present study, we examined the mechanism by which α-LA activates the Nrf2/HO-1 pathway, suppresses the production of pro-inflammatory cytokine interleukine-8 (IL-8), and reduces reactive oxygen species (ROS) in H. pylori-infected AGS cells. α-LA increased the level of phosphorylated and nuclear-translocated Nrf2 by decreasing the amount of Nrf2 sequestered in the cytoplasm by complex formation with Kelch-like ECH1-associated protein 1 (KEAP 1). By using exogenous inhibitors targeting Nrf2 and HO-1, we showed that up-regulation of activated Nrf2 and of HO-1 results in the α-LA-induced suppression of interleukin 8 (IL-8) and ROS. Consumption of α-LA-rich foods may prevent the development of H. pylori-associated gastric diseases by decreasing ROS-mediated IL-8 expression in gastric epithelial cells.
Highlights
Introduction α-Lipoic acid (α-LA) is an endogenous dithiol found in small quantities in all foods but is slightly enriched in spinach, broccoli and some meats [1]. α-LA is widely used as a dietary supplement because it is regarded as an ideal antioxidant agent owing to its ability to scavenge free radicals, chelate transition metal ions, and up-regulate the expression of antioxidant genes [2]. α-LA has been shown to confer a protective effect against various diseases, including Alzheimer’s disease and diabetes [3,4,5,6]
In previous work focusing on the effect of α-LA on Helicobacter pylori (H. pylori) infection-induced oxidative stress in gastric epithelial cells, we showed that α-LA decreases reactive oxygen species (ROS) levels and suppresses
We have focused on the effect of α-LA on nuclear factor erythroid 2-related factor 2 (Nrf2), which is a crucial
Summary
Introduction αLipoic acid (α-LA) is an endogenous dithiol found in small quantities in all foods but is slightly enriched in spinach, broccoli and some meats [1]. α-LA is widely used as a dietary supplement because it is regarded as an ideal antioxidant agent owing to its ability to scavenge free radicals, chelate transition metal ions, and up-regulate the expression of antioxidant genes [2]. α-LA has been shown to confer a protective effect against various diseases, including Alzheimer’s disease and diabetes [3,4,5,6]. Α-LA has been shown to confer a protective effect against various diseases, including Alzheimer’s disease and diabetes [3,4,5,6]. In previous work focusing on the effect of α-LA on Helicobacter pylori (H. pylori) infection-induced oxidative stress in gastric epithelial cells, we showed that α-LA decreases ROS levels and suppresses. NADPH oxidase activity and the inflammatory signaling pathways mediated by mitogen-activated protein kinases, janus kinase/signal transducers and activators of transcription (JAK/STAT) and nuclear factor kappa light chain enhancer of activated B cells (NF-kB) [7,8]. We have focused on the effect of α-LA on nuclear factor erythroid 2-related factor 2 (Nrf2), which is a crucial. Nrf is retained in the cytoplasm at low levels by the redox-sensor Kelch-like ECH-associated protein 1 (KEAP 1), which in turn facilitates Nrf ubiquitination and subsequent degradation [10]
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