The Unusual Amino Acid L-Ergothioneine is a Physiologic Cytoprotectant
ET [Ergothioneine] is a most unusual amino acid with substantial antioxidant efficacy. The existence of a physiologic ET transporter [ETT] is responsible for high tissue levels. Depletion of ETT leads to augmented oxidative stress and cell death. ET preferentially protects water soluble proteins from oxidative damage.
This study provides substantial evidence that ET is a physiologic antioxidant cytoprotectant. ET tissue levels are maintained by its transporter, ETT. Depletion of ETT by RNA interference prevents the antioxidant actions of exogenous ET. More importantly, in the absence of added ET, ETT depletion leads to enhanced oxidative damage of protein, lipid and DNA as well as augmented cell death. In these studies the incubation media contained very low concentrations of ET so that cytoprotection was afforded by ‘endogenous’ ET accumulated by the cells.
The high density of ETT in mitochondria implies a unique role in protecting this organelle from the reactive oxygen species that accumulate even with normal oxidative metabolism. ET also protects the cell from damage induced by reactive nitrogen species and UV radiation. For all these reasons ET appears to be an important physiologic cytoprotectant which probably merits designation as a vitamin.