Potential beneficial effect of ergothioneine in protecting endothelial dysfunction

Abstract

Endothelial function is often impaired in diabetic patients, leading to various pathophysiological processes in cardiovascular diseases. A number of evidence has also demonstrated that reactive oxygen species is one of the major factors for diabetic endothelial dysfunction. Ergothioneine, a chemical rich in mushroom, has been proposed to possess potent antioxidant activities, involving the removal of cell toxic radical species or chelating of metal ions. However, the biological relevance of these findings is unclear because most of the preceding studies were performed in cell-free systems. In this study, we aimed to investigate if ergothioneine can enter endothelial cells and protect endothelial cells against diabetes-induced damage. Human brain microvascular endothelial cells (HBMECs) were used in this study. Ergothioneine is a transport substrate of organic cation transporter novel type 1 (OCTN-1) and our result of RT-PCR and Western blotting showed that OCTN-1 was present in HBMECs. HBMECs were incubated in 5 mM (control) and 25 mM glucose medium (which mimicked the hyperglycemia in diabetes) in the absence of presence of ergothioneine. By means of MTT assay, we found that the viability of HBMECs was significantly lowered in 25 mM glucose condition but this detrimental effect of high glucose could be reduced by ergothioneine, at a concentration as low as 10 nM. In conclusion, our result suggests that ergothioneine can be taken up by endothelial cells and may be a potential protective agent that can protect endothelial cells, particularly in the case of diabetes