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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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the Society for Free Radical Research Japan
2016
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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 |
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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 |
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