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Yinuo, W.* ; Toyama, T.* ; Yamakoshi, H.* ; Taguchi, H.* ; Takashima, H.* ; Watanabe, R.* ; Mita, Y.* ; Ito, J. ; Mishima, E. ; Akiyama, Y.* ; Shibata, H.* ; Noguchi, N.* ; Takamura, T.* ; Conrad, M. ; Tomikoka, Y.* ; Iwabuchi, Y.* ; Saito, Y.*

Electrophilic monocarbonyl curcumin derivatives reveal differential vulnerabilities in the selenium metabolic network.

Free Radical Biol. Med. 253, 487-499 (2026)
DOI PMC
Selenium is an essential trace element whose biological functions are exerted through selenoproteins, synthesized by a highly coordinated and redox-regulated network. How this network responds to electrophilic stimulus, however, remains incompletely understood. Here, we employed a focused library of monocarbonyl curcumin derivatives as electrophilic chemical tools to interrogate the selenium metabolic network. Screening based on intracellular selenoprotein P abundance identified GO-Y015 as a potent and low-toxicity compound capable of strongly changing expression of selenoprotein P and glutathione peroxidase. In cultured hepatocytes, GO-Y015 suppressed selenoprotein expression by inhibiting de novo selenoprotein synthesis, rather than promoting lysosomal degradation. Biochemical analyses revealed that GO-Y015 covalently modified multiple selenium-handling enzymes, including PRDX6, SCLY, and SEPHS2, and impaired selenium incorporation into Sec-tRNA, indicating broader alternation of selenium metabolism. Short-term administration of GO-Y015 in mice resulted in a selective reduction of circulating selenoprotein P, with limited effects on other selenoproteins and no overt hepatotoxicity. Under these conditions, no body-weight loss and hepatotoxicity was observed, supporting the interpretation that the observed molecular effects reflect acute metabolic alteration. Together, these findings establish electrophilic monocarbonyl curcumin derivatives as chemical tools that reveal differential vulnerabilities within the selenium metabolic network, with selenoprotein P serving as a particularly sensitive indicator of selenium metabolic modulation.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Selenium ; Curcumin ; Electrophile ; Differential (mechanical Device) ; Metabolic Pathway
ISSN (print) / ISBN 0891-5849
e-ISSN 1873-4596
Zeitschrift Free Radical Biology and Medicine
Quellenangaben Band: 253, Heft: , Seiten: 487-499 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort New York, NY
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Metabolism and Cell Death (MCD)