@article{TurriniKroepflJensenetal.2018,
  author    = {Turrini, Nikolaus G. and Kroepfl, Nina and Jensen, Kenneth Bendix and Reiter, Tamara C. and Francesconi, Kevin A. and Schwerdtle, Tanja and Kroutil, Wolfgang and Kuehnelt, Doris},
  title     = {Biosynthesis and isolation of selenoneine from genetically modified fission yeast},
  series = {Metallomics : integrated biometal science},
  volume    = {10},
  journal   = {Metallomics : integrated biometal science},
  number    = {10},
  publisher = {Royal Society of Chemistry},
  address   = {Cambridge},
  issn      = {1756-5901},
  doi       = {10.1039/c8mt00200b},
  pages     = {1532 -- 1538},
  year      = {2018},
  abstract  = {Selenoneine, a naturally occurring form of selenium, is the selenium analogue of ergothioneine, a sulfur species with health relevance not only as a purported antioxidant but likely also beyond. Selenoneine has been speculated to exhibit similar effects. To study selenoneine's health properties as well as its metabolic transformation, the pure compound is required. Chemical synthesis of selenoneine, however, is challenging and biosynthetic approaches have been sought. We herein report the biosynthesis and isolation of selenoneine from genetically modified fission yeast Schizosaccharomyces pombe grown in a medium containing sodium selenate. After cell lysis and extraction with methanol, selenoneine was purified by three consecutive preparative reversed-phase HPLC steps. The product obtained at the mg level was characterised by high resolution mass spectrometry, NMR and HPLC/ICPMS. Biosynthesis was found to be a promising alternative to chemical synthesis, and should be suitable for upscaling to produce higher amounts of this important selenium species in the future.},
  language  = {en}
}
@article{KroepflFrancesconiSchwerdtleetal.2019,
  author    = {Kroepfl, Nina and Francesconi, Kevin A. and Schwerdtle, Tanja and Kuehnelt, Doris},
  title     = {Selenoneine and ergothioneine in human blood cells determined simultaneously by HPLC/ICP-QQQ-MS},
  series = {Journal of Analytical Atomic Spectrometry},
  volume    = {34},
  journal   = {Journal of Analytical Atomic Spectrometry},
  number    = {1},
  publisher = {Royal Society of Chemistry},
  address   = {Cambridge},
  issn      = {0267-9477},
  doi       = {10.1039/c8ja00276b},
  pages     = {127 -- 134},
  year      = {2019},
  abstract  = {The possible relevance to human health of selenoneine and its sulfur-analogue ergothioneine has generated interest in their quantitative determination in biological samples. To gain more insight into the similarities and differences of these two species, a method for their simultaneous quantitative determination in human blood cells using reversed-phase high performance liquid chromatography (RP-HPLC) coupled to inductively coupled plasma triple quadrupole mass spectrometry (ICP-QQQ-MS) is presented. Spectral interferences hampering the determination of sulfur and selenium by ICPMS are overcome by introducing oxygen to the reaction cell. To access selenoneine and ergothioneine in the complex blood matrix, lysis of the cells with cold water followed by cut-off filtration (3000 Da) is performed. Recoveries based on blood cells spiked with selenoneine and ergothioneine were between 80\% and 85\%. The standard deviation of the method was around 0.10 mg S per L for ergothioneine (corresponding to relative standard deviations (RSD) between 10-1\% for ergothioneine concentrations of 1-10 mg S per L) and 0.25 g Se per L for selenoneine (RSDs of 25-2\% for concentrations of 1-10 g Se per L). The method was applied to blood cell samples from three volunteers which showed selenoneine and ergothioneine concentrations in the range of 3.25 to 7.35 g Se per L and 0.86 to 6.44 mg S per L, respectively. The method is expected to be of wide use in future studies investigating the dietary uptake of selenoneine and ergothioneine and their relevance in human health.},
  language  = {en}
}
@article{MarschallKroepflJensenetal.2017,
  author    = {Marschall, Talke Anu and Kroepfl, Nina and Jensen, Kenneth Bendix and Bornhorst, Julia and Meermann, B. and K{\"u}hnelt, Doris and Schwerdtle, Tanja},
  title     = {Tracing cytotoxic effects of small organic Se species in human liver cells back to total cellular Se and Se metabolites},
  series = {Metallomics},
  volume    = {9},
  journal   = {Metallomics},
  publisher = {Royal Society of Chemistry},
  address   = {Cambridge},
  issn      = {1756-5901},
  doi       = {10.1039/c6mt00300a},
  pages     = {268 -- 277},
  year      = {2017},
  abstract  = {Small selenium (Se) species play a major role in the metabolism, excretion and dietary supply of the essential trace element selenium. Human cells provide a valuable tool for investigating currently unresolved issues on the cellular mechanisms of Se toxicity and metabolism. In this study, we developed two isotope dilution inductively coupled plasma tandem-mass spectrometry based methods and applied them to human hepatoma cells (HepG2) in order to quantitatively elucidate total cellular Se concentrations and cellular Se species transformations in relation to the cytotoxic effects of four small organic Se species. Species-and incubation time-dependent results were obtained: the two major urinary excretion metabolites trimethylselenonium (TMSe) and methyl-2-acetamido-2-deoxy-1-seleno-beta- D-galactopyranoside (SeSugar 1) were taken up by the HepG2 cells in an unmodified manner and did not considerably contribute to the Se pool. In contrast, Se-methylselenocysteine (MeSeCys) and selenomethionine (SeMet) were taken up in higher amounts, they were largely incorporated by the cells (most likely into proteins) and metabolized to other small Se species. Two new metabolites of MeSeCys, namely gamma-glutamyl-Se-methylselenocysteine and Se-methylselenoglutathione, were identified by means of HPLC-electrospray-ionization-Orbitrap-MS. They are certainly involved in the (de-) toxification modes of Se metabolism and require further investigation.},
  language  = {en}
}
@article{RohnKroepflAschneretal.2019,
  author    = {Rohn, Isabelle and Kroepfl, Nina and Aschner, Michael and Bornhorst, Julia and Kuehnelt, Doris and Schwerdtle, Tanja},
  title     = {Selenoneine ameliorates peroxide-induced oxidative stress in C. elegans},
  series = {Journal of trace elements in medicine and biology},
  volume    = {55},
  journal   = {Journal of trace elements in medicine and biology},
  publisher = {Elsevier GMBH},
  address   = {M{\"u}nchen},
  issn      = {0946-672X},
  doi       = {10.1016/j.jtemb.2019.05.012},
  pages     = {78 -- 81},
  year      = {2019},
  abstract  = {Scope: Selenoneine (2-selenyl-N-alpha, N-alpha, N-alpha-trimethyl-L-histidine), the selenium (Se) analogue of the ubiquitous thiol compound and putative antioxidant ergothioneine, is the major organic selenium species in several marine fish species. Although its antioxidant efficacy has been proposed, selenoneine has been poorly characterized, preventing conclusions on its possible beneficial health effects. Methods and results: Treatment of Caenorhabditis elegans (C. elegans) with selenoneine for 18 h attenuated the induction of reactive oxygen and nitrogen species (RONS). However, the effect was not immediate, occurring 48 h post-treatment. Total Se and Se speciation analysis revealed that selenoneine was efficiently taken up and present in its original form directly after treatment, with no metabolic transformations observed. 48 h posttreatment, total Se in worms was slightly higher compared to controls and no selenoneine could be detected. Conclusion: The protective effect of selenoneine may not be attributed to the presence of the compound itself, but rather to the activation of molecular mechanisms with consequences at more protracted time points.},
  language  = {en}
}
@article{RohnKroepflBornhorstetal.2019,
  author    = {Rohn, Isabelle and Kroepfl, Nina and Bornhorst, Julia and K{\"u}hnelt, Doris and Schwerdtle, Tanja},
  title     = {Side-directed transfer and presystemic metabolism of selenoneine in a human intestinal barrier model},
  series = {Molecular nutrition \& food research : bioactivity, chemistry, immunology, microbiology, safety, technology},
  volume    = {63},
  journal   = {Molecular nutrition \& food research : bioactivity, chemistry, immunology, microbiology, safety, technology},
  number    = {12},
  publisher = {Wiley},
  address   = {Hoboken},
  issn      = {1613-4125},
  doi       = {10.1002/mnfr.201900080},
  pages     = {11},
  year      = {2019},
  abstract  = {Scope: Selenoneine, a recently discovered selenium (Se) species mainly present in marine fish, is the Se analogue of ergothioneine, a sulfur-containing purported antioxidant. Although similar properties have been proposed for selenoneine, data on its relevance to human health are yet scarce. Here, the transfer and presystemic metabolism of selenoneine in an in vitro model of the human intestinal barrier are investigated. Methods and results: Selenoneine and the reference species Se-methylselenocysteine (MeSeCys) and selenite are applied to the Caco-2 intestinal barrier model. Selenoneine is transferred in higher amounts, but with similar kinetics as selenite, while MeSeCys shows the highest permeability. In contrast to the reference species, transfer of selenoneine is directed toward the blood side. Cellular Se contents demonstrate that selenoneine is efficiently taken up by Caco-2 cells. Moreover, HPLC/MS-based Se speciation studies reveal a partial metabolism to Se-methylselenoneine, a metabolite previously detected in human blood and urine. Conclusions: Selenoneine is likely to pass the intestinal barrier via transcellular, carrier-mediated transport, is highly bioavailable to Caco-2 cells and undergoes metabolic transformations. Therefore, further studies are needed to elucidate its possible health effects and to characterize the metabolism of selenoneine in humans.},
  language  = {en}
}