Epo-C12 inhibits peroxiredoxin 1 peroxidase activity

  • Bioorg Med Chem. 2021 Jul 1:41:116203. doi: 10.1016/j.bmc.2021.116203.
Tomoka Yoda  1 ,  Masateru Furuta  1 ,  Tomohiko Tsutsumi  1 ,  Seiki Ikeda  1 ,  Shunsuke Yukizawa  1 ,  Satoshi Arai  1 ,  Akinori Morita  2 ,  Kenji Yamatoya  3 ,  Kazuya Nakata  4 ,  Shusuke Tomoshige  5 ,  Kenji Ohgane  1 ,  Yuuki Furuyama  1 ,  Kengo Sakaguchi  1 ,  Fumio Sugawara  1 ,  Susumu Kobayashi  6 ,  Masahiko Ikekita  1 ,  Kouji Kuramochi  7
Affiliations
  • 1. Department of Applied Biological Science, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
  • 2. Department of Applied Biological Science, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan; Department of Biomedical Science and Technology, Graduate School of Biomedical Sciences, Tokushima University, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan.
  • 3. Department of Applied Biological Science, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan; Institute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu-City, Chiba, 279-0021, Japan.
  • 4. Department of Applied Biological Science, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan; Graduate School of Bio-Applications and Systems Engineering, Tokyo University of Agriculture and Technology, 2-24-16 Nakacho, Koganei, Tokyo, 184-0012, Japan.
  • 5. Department of Applied Biological Science, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan; Graduate School of Life Sciences, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577, Japan.
  • 6. Department of Pharmacy, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
  • 7. Department of Applied Biological Science, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan. Electronic address: [email protected].
PMID: 34015702 DOI: 10.1016/j.bmc.2021.116203
Abstract

Epo-C12 is a synthetic derivative of epolactaene, isolated from Penicillium sp. BM 1689-P. Epo-C12 induces Apoptosis in human acute lymphoblastoid leukemia BALL-1 cells. In our previous studies, seven proteins that bind to Epo-C12 were identified by a combination of pull-down experiments using biotinylated Epo-C12 (Bio-Epo-C12) and mass spectrometry. In the present study, the effect of Epo-C12 on peroxiredoxin 1 (Prx 1), one of the proteins that binds to Epo-C12, was investigated. Epo-C12 inhibited Prx 1 peroxidase activity. However, it did not suppress its chaperone activity. Binding experiments between Bio-Epo-C12 and point-mutated Prx 1s suggest that Epo-C12 binds to Cys52 and Cys83 in Prx 1. The present study revealed that Prx 1 is one of the target proteins through which Epo-C12 exerts an apoptotic effect in BALL-1 cells.

Keywords
Chaperone; Epolactaene; Peroxidase; Peroxiredoxin 1; Reactive oxygen species.