TY - JOUR
T1 - The unusual amino acid L-ergothioneine is a physiologic cytoprotectant
AU - Paul, B. D.
AU - Snyder, S. H.
N1 - Funding Information:
Acknowledgements. This work was supported by United States Public Health Service Grants DA00266 (to SHS) and a Research Scientist Award DA00074 (to SHS).
PY - 2010/7
Y1 - 2010/7
N2 - Ergothioneine (ET) is an unusual sulfur-containing derivative of the amino acid, histidine, which is derived exclusively through the diet. Although ET was isolated a century ago, its physiologic function has not been clearly established. Recently, a highly specific transporter for ET (ETT) was identified in mammalian tissues, which explains abundant tissue levels of ET and implies a physiologic role. Using RNA interference, we depleted cells of its transporter. Cells lacking ETT are more susceptible to oxidative stress, resulting in increased mitochondrial DNA damage, protein oxidation and lipid peroxidation. ETT is concentrated in mitochondria, suggesting a specific role in protecting mitochondrial components such as DNA from oxidative damage associated with mitochondrial generation of superoxide. In combating cytotoxic effects of pyrogallol, a known superoxide generator, ET is as potent as glutathione. Because of its dietary origin and the toxicity associated with its depletion, ET may represent a new vitamin whose physiologic roles include antioxidant cytoprotection.
AB - Ergothioneine (ET) is an unusual sulfur-containing derivative of the amino acid, histidine, which is derived exclusively through the diet. Although ET was isolated a century ago, its physiologic function has not been clearly established. Recently, a highly specific transporter for ET (ETT) was identified in mammalian tissues, which explains abundant tissue levels of ET and implies a physiologic role. Using RNA interference, we depleted cells of its transporter. Cells lacking ETT are more susceptible to oxidative stress, resulting in increased mitochondrial DNA damage, protein oxidation and lipid peroxidation. ETT is concentrated in mitochondria, suggesting a specific role in protecting mitochondrial components such as DNA from oxidative damage associated with mitochondrial generation of superoxide. In combating cytotoxic effects of pyrogallol, a known superoxide generator, ET is as potent as glutathione. Because of its dietary origin and the toxicity associated with its depletion, ET may represent a new vitamin whose physiologic roles include antioxidant cytoprotection.
KW - Antioxidant
KW - Histidine derivative
KW - Mitochondrial DNA
KW - Reactive oxygen species
KW - Superoxide
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U2 - 10.1038/cdd.2009.163
DO - 10.1038/cdd.2009.163
M3 - Article
C2 - 19911007
AN - SCOPUS:77953620630
SN - 1350-9047
VL - 17
SP - 1134
EP - 1140
JO - Cell death and differentiation
JF - Cell death and differentiation
IS - 7
ER -