Cargando…

Lipid peroxides as endogenous oxidants forming 8-oxo-guanosine and lipid-soluble antioxidants as suppressing agents

The oxidation of guanosine to 8-oxo-2'-deoxyguanosine (8-oxo-dG) in DNA is closely associated with induction of various diseases, but the endogenous oxidant species involved remains unclear. Hydrogen peroxides (H(2)O(2)) have been considered to be the oxidant, while lipid peroxides are another...

Descripción completa

Detalles Bibliográficos
Autores principales: Kanazawa, Kazuki, Sakamoto, Miku, Kanazawa, Ko, Ishigaki, Yoriko, Aihara, Yoshiko, Hashimoto, Takashi, Mizuno, Masashi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: the Society for Free Radical Research Japan 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4933685/
https://www.ncbi.nlm.nih.gov/pubmed/27499574
http://dx.doi.org/10.3164/jcbn.15-122
_version_ 1782441206243917824
author Kanazawa, Kazuki
Sakamoto, Miku
Kanazawa, Ko
Ishigaki, Yoriko
Aihara, Yoshiko
Hashimoto, Takashi
Mizuno, Masashi
author_facet Kanazawa, Kazuki
Sakamoto, Miku
Kanazawa, Ko
Ishigaki, Yoriko
Aihara, Yoshiko
Hashimoto, Takashi
Mizuno, Masashi
author_sort Kanazawa, Kazuki
collection PubMed
description The oxidation of guanosine to 8-oxo-2'-deoxyguanosine (8-oxo-dG) in DNA is closely associated with induction of various diseases, but the endogenous oxidant species involved remains unclear. Hydrogen peroxides (H(2)O(2)) have been considered to be the oxidant, while lipid peroxides are another possible oxidant because generated easily in bio-membranes surrounding DNA. The oxidant potency was compared between lipid peroxides and H(2)O(2). Linoleic acid hydroperoxides (LOOH) formed 8-oxo-dG at a higher level than H(2)O(2) in guanosine or double-stranded DNA. In the presence of a physiological concentration of Fe(2+) to produce hydroxyl radicals, LOOH was also a stronger oxidant. In a lipid micelle, LOOH markedly produced 8-oxo-dG at a concentration one-tenth of that of H(2)O(2). Upon adding to rat hepatic mitochondria, phosphatidylcholine hydroperoxides produced 8-oxo-dG abundantly. Employing HepG2 cells after pretreated with glutathione peroxidase inhibitor, LOOH formed 8-oxo-dG more abundantly than H(2)O(2). Then, antioxidants to suppress the 8-oxo-dG formation were examined, when the nuclei of pre-incubated HepG2 with antioxidants were exposed to LOOH. Water-soluble ascorbic acid, trolox, and N-acetyl cysteine showed no or weak antioxidant potency, while lipid-soluble 2,6-dipalmitoyl ascorbic acid, α-tocopherol, and lipid-soluble phytochemicals exhibited stronger potency. The present study shows preferential formation of 8-oxo-dG upon LOOH and the inhibition by lipid-soluble antioxidants.
format Online
Article
Text
id pubmed-4933685
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher the Society for Free Radical Research Japan
record_format MEDLINE/PubMed
spelling pubmed-49336852016-08-05 Lipid peroxides as endogenous oxidants forming 8-oxo-guanosine and lipid-soluble antioxidants as suppressing agents Kanazawa, Kazuki Sakamoto, Miku Kanazawa, Ko Ishigaki, Yoriko Aihara, Yoshiko Hashimoto, Takashi Mizuno, Masashi J Clin Biochem Nutr Original Article The oxidation of guanosine to 8-oxo-2'-deoxyguanosine (8-oxo-dG) in DNA is closely associated with induction of various diseases, but the endogenous oxidant species involved remains unclear. Hydrogen peroxides (H(2)O(2)) have been considered to be the oxidant, while lipid peroxides are another possible oxidant because generated easily in bio-membranes surrounding DNA. The oxidant potency was compared between lipid peroxides and H(2)O(2). Linoleic acid hydroperoxides (LOOH) formed 8-oxo-dG at a higher level than H(2)O(2) in guanosine or double-stranded DNA. In the presence of a physiological concentration of Fe(2+) to produce hydroxyl radicals, LOOH was also a stronger oxidant. In a lipid micelle, LOOH markedly produced 8-oxo-dG at a concentration one-tenth of that of H(2)O(2). Upon adding to rat hepatic mitochondria, phosphatidylcholine hydroperoxides produced 8-oxo-dG abundantly. Employing HepG2 cells after pretreated with glutathione peroxidase inhibitor, LOOH formed 8-oxo-dG more abundantly than H(2)O(2). Then, antioxidants to suppress the 8-oxo-dG formation were examined, when the nuclei of pre-incubated HepG2 with antioxidants were exposed to LOOH. Water-soluble ascorbic acid, trolox, and N-acetyl cysteine showed no or weak antioxidant potency, while lipid-soluble 2,6-dipalmitoyl ascorbic acid, α-tocopherol, and lipid-soluble phytochemicals exhibited stronger potency. The present study shows preferential formation of 8-oxo-dG upon LOOH and the inhibition by lipid-soluble antioxidants. the Society for Free Radical Research Japan 2016-07 2016-06-10 /pmc/articles/PMC4933685/ /pubmed/27499574 http://dx.doi.org/10.3164/jcbn.15-122 Text en Copyright © 2016 JCBN This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Kanazawa, Kazuki
Sakamoto, Miku
Kanazawa, Ko
Ishigaki, Yoriko
Aihara, Yoshiko
Hashimoto, Takashi
Mizuno, Masashi
Lipid peroxides as endogenous oxidants forming 8-oxo-guanosine and lipid-soluble antioxidants as suppressing agents
title Lipid peroxides as endogenous oxidants forming 8-oxo-guanosine and lipid-soluble antioxidants as suppressing agents
title_full Lipid peroxides as endogenous oxidants forming 8-oxo-guanosine and lipid-soluble antioxidants as suppressing agents
title_fullStr Lipid peroxides as endogenous oxidants forming 8-oxo-guanosine and lipid-soluble antioxidants as suppressing agents
title_full_unstemmed Lipid peroxides as endogenous oxidants forming 8-oxo-guanosine and lipid-soluble antioxidants as suppressing agents
title_short Lipid peroxides as endogenous oxidants forming 8-oxo-guanosine and lipid-soluble antioxidants as suppressing agents
title_sort lipid peroxides as endogenous oxidants forming 8-oxo-guanosine and lipid-soluble antioxidants as suppressing agents
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4933685/
https://www.ncbi.nlm.nih.gov/pubmed/27499574
http://dx.doi.org/10.3164/jcbn.15-122
work_keys_str_mv AT kanazawakazuki lipidperoxidesasendogenousoxidantsforming8oxoguanosineandlipidsolubleantioxidantsassuppressingagents
AT sakamotomiku lipidperoxidesasendogenousoxidantsforming8oxoguanosineandlipidsolubleantioxidantsassuppressingagents
AT kanazawako lipidperoxidesasendogenousoxidantsforming8oxoguanosineandlipidsolubleantioxidantsassuppressingagents
AT ishigakiyoriko lipidperoxidesasendogenousoxidantsforming8oxoguanosineandlipidsolubleantioxidantsassuppressingagents
AT aiharayoshiko lipidperoxidesasendogenousoxidantsforming8oxoguanosineandlipidsolubleantioxidantsassuppressingagents
AT hashimototakashi lipidperoxidesasendogenousoxidantsforming8oxoguanosineandlipidsolubleantioxidantsassuppressingagents
AT mizunomasashi lipidperoxidesasendogenousoxidantsforming8oxoguanosineandlipidsolubleantioxidantsassuppressingagents