Browsing by Author "Motohashi, Hozumi"

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    Comment on “Evidence that the ProPerDP method is inadequate for protein persulfidation detection due to lack of specificity”
    (American Association for the Advancement of Science, 2021-04-21) Dóka, Éva; Arnér, Elias S.J.; Schmidt, Edward E.; Dick, Tobias P.; van der Vliet, Albert; Yang, Jing; Szatmári, Réka; Ditrói, Tamás; Wallace, John L.; Cirino, Giuseppe; Olson, Kenneth; Motohashi, Hozumi; Fukuto, Jon M.; Pluth, Michael D.; Feelisch, Martin; Akaike, Takaaki; Wink, David A.; Ignarro, Louis J.; Nagy, Péter; Medicine, School of Medicine
    The recent report by Fan et al. alleged that the ProPerDP method is inadequate for the detection of protein persulfidation. Upon careful evaluation of their work, we conclude that the claim made by Fan et al. is not supported by their data, rather founded in methodological shortcomings. It is understood that the ProPerDP method generates a mixture of cysteine-containing and non–cysteine-containing peptides. Instead, Fan et al. suggested that the detection of non–cysteine-containing peptides indicates nonspecific alkylation at noncysteine residues. However, if true, then such peptides would not be released by reduction and therefore not appear as products in the reported workflow. Moreover, the authors’ biological assessment of ProPerDP using Escherichia coli mutants was based on assumptions that have not been confirmed by other methods. We conclude that Fan et al. did not rigorously assess the method and that ProPerDP remains a reliable approach for analyses of protein per/polysulfidation.
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    Health position paper and redox perspectives - Bench to bedside transition for pharmacological regulation of NRF2 in noncommunicable diseases
    (Elsevier, 2025) Cuadrado, Antonio; Cazalla, Eduardo; Bach, Anders; Bathish, Boushra; Naidu, Sharadha Dayalan; DeNicola, Gina M.; Dinkova-Kostova, Albena T.; Fernández-Ginés, Raquel; Grochot-Przeczek, Anna; Hayes, John D.; Kensler, Thomas W.; León, Rafael; Liby, Karen T.; López, Manuela G.; Manda, Gina; Shivakumar, Akshatha Kalavathi; Hakomäki, Henriikka; Moerland, Jessica A.; Motohashi, Hozumi; Rojo, Ana I.; Sykiotis, Gerasimos P.; Taguchi, Keiko; Valverde, Ángela M.; Yamamoto, Masayuki; Levonen, Anna-Liisa; Medicine, School of Medicine
    Nuclear factor erythroid 2-related factor 2 (NRF2) is a redox-activated transcription factor regulating cellular defense against oxidative stress, thereby playing a pivotal role in maintaining cellular homeostasis. Its dysregulation is implicated in the progression of a wide array of human diseases, making NRF2 a compelling target for therapeutic interventions. However, challenges persist in drug discovery and safe targeting of NRF2, as unresolved questions remain especially regarding its context-specific role in diseases and off-target effects. This comprehensive review discusses the dualistic role of NRF2 in disease pathophysiology, covering its protective and/or destructive roles in autoimmune, respiratory, cardiovascular, and metabolic diseases, as well as diseases of the digestive system and cancer. Additionally, we also review the development of drugs that either activate or inhibit NRF2, discuss main barriers in translating NRF2-based therapies from bench to bedside, and consider the ways to monitor NRF2 activation in vivo.