The unusual amino acid L-ergothioneine is a physiologic cytoprotectant.
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.
Paul
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The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Snyder
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D000975:Antioxidants / Q000494:pharmacology*; D019610:Cytoprotection / Q000187:drug effects*; D004249:DNA Damage; D004880:Ergothioneine / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D015227:Lipid Peroxidation; D008928:Mitochondria / Q000378:metabolism; D027701:Organic Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D034622:RNA Interference; D017382:Reactive Oxygen Species / Q000378:metabolism; D027981:Symporters
D000975:Antioxidants; D027701:Organic Cation Transport Proteins; D017382:Reactive Oxygen Species; C109807:SLC22A4 protein, human; D027981:Symporters; D004880:Ergothioneine