Abstract:
:Tropolones, the naturally occurring compounds responsible for the durability of heartwood of several cupressaceous trees, have been shown to possess both metal chelating and antioxidant properties. However, little is known about the ability of tropolone and its derivatives to protect cultured cells from oxidative stress-mediated damage. In this study, the effect of tropolones on hydrogen peroxide-induced DNA damage and apoptosis was investigated in cultured Jurkat cells. Tropolone, added to the cells 15 min before the addition of glucose oxidase, provided a dose dependent protection against hydrogen peroxide induced DNA damage. The IC50 value observed was about 15 microM for tropolone. Similar dose dependent protection was also observed with three other tropolone derivatives such as trimethylcolchicinic acid, purpurogallin and beta-thujaplicin (the IC50 values were 34, 70 and 74 microM, respectively), but not with colchicine and tetramethyl purpurogallin ester. Hydrogen peroxide-induced apoptosis was also inhibited by tropolone. However, in the absence of exogenous H2O2 but in the presence of non-toxic concentrations of exogenous iron (100 microM Fe3+), tropolone dramatically increased the formation of single strand breaks at molar ratios of tropolone to iron lower than 3 to 1, while, when the ratio increased over 3, no toxicity was observed. In conclusion, the results presented in this study indicate that the protection offered by tropolone against hydrogen peroxide-induced DNA damage and apoptosis was due to formation of a redox-inactive iron complex, while its enhancement of iron-mediated DNA damage at ratios of [tropolone]/[Fe3+] lower than 3, was due to formation of a lipophilic iron complex which facilitates iron transport through cell membrane in a redox-active form.
journal_name
Free Radic Resjournal_title
Free radical researchauthors
Doulias PT,Nousis L,Zhu BZ,Frei B,Galaris Ddoi
10.1080/10715760400017244keywords:
subject
Has Abstractpub_date
2005-02-01 00:00:00pages
125-35issue
2eissn
1071-5762issn
1029-2470pii
N2DCP2KYGYHKC3AHjournal_volume
39pub_type
杂志文章abstract::Intracellular levels of H2O2 in BHK-21 cells are not static but decline progressively with cell growth. Exposure of cells to inhibitors of catalase, or glutathione peroxidase, not only diminishes this decline but also depresses rates of cell proliferation, suggesting important growth regulatory roles for those antioxi...
journal_title:Free radical research
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journal_title:Free radical research
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更新日期:1998-01-01 00:00:00
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更新日期:2015-03-01 00:00:00
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更新日期:2012-10-01 00:00:00
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更新日期:2000-09-01 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2013-08-01 00:00:00
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journal_title:Free radical research
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更新日期:2016-11-01 00:00:00
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更新日期:2004-10-01 00:00:00
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doi:10.1080/10715760000301301
更新日期:2000-12-01 00:00:00
abstract::Peroxiredoxin 1 (PRDX1) is an antioxidant enzyme that, when secreted, can act as a proinflammatory signal. Here we studied the regulation of intracellular PRDX1 by lipopolysaccharide (LPS) and interferon-gamma (IFN-γ) in the RAW 264.7 mouse macrophage cell line. While LPS or IFN-γ alone did not affect PRDX1 protein le...
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