The Effect of ERK Signaling Pathway on the Level of Soluble RAGE (sRAGE) Peptide in AGE-Induced Oxidative Stress

Abstract

In the context of diabetes, there is a bidirectional relation between AGEs and ROS which is amplified under hyperglycemic condition. Indeed, the AGE/RAGE interaction, via triggering several signaling pathways underlies such interplay. These damaging signaling cascades could be attenuated by naturally occurring soluble form of RAGE, namely sRAGE. In the present study, the effect of AGEs on the intracellular superoxide anion level and the antioxidant defense system was studied. Moreover, the link between the level of soluble RAGE and the AGE-triggered signaling pathways, namely ERK, was also investigated. Our results demonstrated that the elevation in intracellular superoxide anion level was associated with decrease in antioxidant enzyme activities. Our data also revealed that the level of sRAGE is negatively correlated with the ERK expression in a hyperglycemia model system. Hence, the current study brings about novel evidences suggesting that the level of sRAGE would be under the influence of stress-sensitive signaling pathways. Highlights • Prominent activity decrease of intracellular antioxidant enzymes was demonstrated upon AGE-treatment. • An increase in superoxide anion level was demonstrated upon AGE-treatment. • The level of sRAGE is negatively associated with the ERK expression in AGE-treated cells. • The level of sRAGE was shown to significantly elevate in the presence of ERK inhibitor.

Keywords

• advanced glycation end products
• erk signaling pathway
• reactive oxygen specious
• soluble receptor