Cargando…

Comparison of Ferroptosis-Inhibitory Mechanisms between Ferrostatin-1 and Dietary Stilbenes (Piceatannol and Astringin)

Synthetic arylamines and dietary phytophenolics could inhibit ferroptosis, a recently discovered regulated cell death process. However, no study indicates whether their inhibitory mechanisms are inherently different. Herein, the ferroptosis-inhibitory mechanisms of selected ferrostatin-1 (Fer-1) and...

Descripción completa

Detalles Bibliográficos
Autores principales: Chen, Ban, Li, Xican, Ouyang, Xiaojian, Liu, Jie, Liu, Yangping, Chen, Dongfeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922211/
https://www.ncbi.nlm.nih.gov/pubmed/33669598
http://dx.doi.org/10.3390/molecules26041092
_version_ 1783658638185857024
author Chen, Ban
Li, Xican
Ouyang, Xiaojian
Liu, Jie
Liu, Yangping
Chen, Dongfeng
author_facet Chen, Ban
Li, Xican
Ouyang, Xiaojian
Liu, Jie
Liu, Yangping
Chen, Dongfeng
author_sort Chen, Ban
collection PubMed
description Synthetic arylamines and dietary phytophenolics could inhibit ferroptosis, a recently discovered regulated cell death process. However, no study indicates whether their inhibitory mechanisms are inherently different. Herein, the ferroptosis-inhibitory mechanisms of selected ferrostatin-1 (Fer-1) and two dietary stilbenes (piceatannol and astringin) were compared. Cellular assays suggested that the ferroptosis-inhibitory and electron-transfer potential levels decreased as follows: Fer-1 >> piceatannol > astringin; however, the hydrogen-donating potential had an order different from that observed by the antioxidant experiments and quantum chemistry calculations. Quantum calculations suggested that Fer-1 has a much lower ionization potential than the two stilbenes, and the aromatic N-atoms were surrounded by the largest electron clouds. By comparison, the C4′O-H groups in the two stilbenes exhibited the lowest bond disassociation enthalpies. Finally, the three were found to produce corresponding dimer peaks through ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry analysis. In conclusion, Fer-1 mainly depends on the electron transfer of aromatic N-atoms to construct a redox recycle. However, piceatannol and astringin preferentially donate hydrogen atoms at the 4′-OH position to mediate the conventional antioxidant mechanism that inhibits ferroptosis, and to ultimately form dimers. These results suggest that dietary phytophenols may be safer ferroptosis inhibitors for balancing normal and ferroptotic cells than arylamines with high electron-transfer potential.
format Online
Article
Text
id pubmed-7922211
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-79222112021-03-03 Comparison of Ferroptosis-Inhibitory Mechanisms between Ferrostatin-1 and Dietary Stilbenes (Piceatannol and Astringin) Chen, Ban Li, Xican Ouyang, Xiaojian Liu, Jie Liu, Yangping Chen, Dongfeng Molecules Article Synthetic arylamines and dietary phytophenolics could inhibit ferroptosis, a recently discovered regulated cell death process. However, no study indicates whether their inhibitory mechanisms are inherently different. Herein, the ferroptosis-inhibitory mechanisms of selected ferrostatin-1 (Fer-1) and two dietary stilbenes (piceatannol and astringin) were compared. Cellular assays suggested that the ferroptosis-inhibitory and electron-transfer potential levels decreased as follows: Fer-1 >> piceatannol > astringin; however, the hydrogen-donating potential had an order different from that observed by the antioxidant experiments and quantum chemistry calculations. Quantum calculations suggested that Fer-1 has a much lower ionization potential than the two stilbenes, and the aromatic N-atoms were surrounded by the largest electron clouds. By comparison, the C4′O-H groups in the two stilbenes exhibited the lowest bond disassociation enthalpies. Finally, the three were found to produce corresponding dimer peaks through ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry analysis. In conclusion, Fer-1 mainly depends on the electron transfer of aromatic N-atoms to construct a redox recycle. However, piceatannol and astringin preferentially donate hydrogen atoms at the 4′-OH position to mediate the conventional antioxidant mechanism that inhibits ferroptosis, and to ultimately form dimers. These results suggest that dietary phytophenols may be safer ferroptosis inhibitors for balancing normal and ferroptotic cells than arylamines with high electron-transfer potential. MDPI 2021-02-19 /pmc/articles/PMC7922211/ /pubmed/33669598 http://dx.doi.org/10.3390/molecules26041092 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chen, Ban
Li, Xican
Ouyang, Xiaojian
Liu, Jie
Liu, Yangping
Chen, Dongfeng
Comparison of Ferroptosis-Inhibitory Mechanisms between Ferrostatin-1 and Dietary Stilbenes (Piceatannol and Astringin)
title Comparison of Ferroptosis-Inhibitory Mechanisms between Ferrostatin-1 and Dietary Stilbenes (Piceatannol and Astringin)
title_full Comparison of Ferroptosis-Inhibitory Mechanisms between Ferrostatin-1 and Dietary Stilbenes (Piceatannol and Astringin)
title_fullStr Comparison of Ferroptosis-Inhibitory Mechanisms between Ferrostatin-1 and Dietary Stilbenes (Piceatannol and Astringin)
title_full_unstemmed Comparison of Ferroptosis-Inhibitory Mechanisms between Ferrostatin-1 and Dietary Stilbenes (Piceatannol and Astringin)
title_short Comparison of Ferroptosis-Inhibitory Mechanisms between Ferrostatin-1 and Dietary Stilbenes (Piceatannol and Astringin)
title_sort comparison of ferroptosis-inhibitory mechanisms between ferrostatin-1 and dietary stilbenes (piceatannol and astringin)
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922211/
https://www.ncbi.nlm.nih.gov/pubmed/33669598
http://dx.doi.org/10.3390/molecules26041092
work_keys_str_mv AT chenban comparisonofferroptosisinhibitorymechanismsbetweenferrostatin1anddietarystilbenespiceatannolandastringin
AT lixican comparisonofferroptosisinhibitorymechanismsbetweenferrostatin1anddietarystilbenespiceatannolandastringin
AT ouyangxiaojian comparisonofferroptosisinhibitorymechanismsbetweenferrostatin1anddietarystilbenespiceatannolandastringin
AT liujie comparisonofferroptosisinhibitorymechanismsbetweenferrostatin1anddietarystilbenespiceatannolandastringin
AT liuyangping comparisonofferroptosisinhibitorymechanismsbetweenferrostatin1anddietarystilbenespiceatannolandastringin
AT chendongfeng comparisonofferroptosisinhibitorymechanismsbetweenferrostatin1anddietarystilbenespiceatannolandastringin