Abstract：
:Leukotoxin (ltx) and isoleukotoxin (iltx) methyl esters, are metabolites of methyl linoleic acid, an essential fatty acid. They have been associated with acute respiratory distress syndrome. The observed toxicity of ltx and iltx is, in fact, due to the metabolism of the epoxides to their corresponding diols by soluble epoxide hydrolase (sEH). Herein, we demonstrate that ltx/iltx are toxic in a time-dependent manner to human sEH expressing cells with a LT(50) of 10.6 +/- 0.8 h and that ltx and iltx have K(M) of 6.15 +/- 1.0 and 5. 17 +/- 0.56 microM, respectively, and V(max) of 2.67 +/- 0.04 and 1. 86 +/- 0.06 micromol/min/mg, respectively, which can be inhibited by sEH inhibitors. We show that four major metabolites of ltx/iltx are formed in our system, including ltx/iltx free acid, ltxd/iltxd, free acid, and phosphotidylcholine and phosphotidylethanolamine containing the carboxylic acid forms of both ltx/iltx and ltxd/iltxd, but that the only metabolite associated with toxicity is the carboxylic acid form of ltxd/iltxd, suggesting the involvement of cellular esterases. We demonstrate that a serine esterase inhibitor provides some protection from the toxicity of epoxy fatty esters to sEH expressing cells as do intercellular free sulfhydryls, but that this protection is not due to glutathione conjugation. With these data, we have proposed an extension of the metabolic pathway for ltx/iltx in eukaryotic cells.
journal_name
Arch Biochem Biophysjournal_title
Archives of biochemistry and biophysicsauthors
Greene JF,Williamson KC,Newman JW,Morisseau C,Hammock BDdoi
10.1006/abbi.2000.1753subject
Has Abstractpub_date
2000-04-15 00:00:00pages
420-32issue
2eissn
0003-9861issn
1096-0384pii
S0003-9861(00)91753-3journal_volume
376pub_type
杂志文章abstract：:The environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces a novel poly(ADP-ribose) polymerase (TiPARP). In this study, the signaling pathway of the induction was analyzed. Induction of TiPARP by TCDD occurs in both hepa1c1c7 cells and C57 mouse liver. Induction is concentration and time dependen...
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journal_title：Archives of biochemistry and biophysics
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journal_title：Archives of biochemistry and biophysics
pub_type： 杂志文章
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journal_title：Archives of biochemistry and biophysics
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journal_title：Archives of biochemistry and biophysics
pub_type： 杂志文章
doi：10.1006/abbi.1994.1034
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journal_title：Archives of biochemistry and biophysics
pub_type： 杂志文章
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doi：10.1006/abbi.1995.1111
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journal_title：Archives of biochemistry and biophysics
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doi：10.1006/abbi.1994.1045
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journal_title：Archives of biochemistry and biophysics
pub_type： 杂志文章
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journal_title：Archives of biochemistry and biophysics
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journal_title：Archives of biochemistry and biophysics
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journal_title：Archives of biochemistry and biophysics
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journal_title：Archives of biochemistry and biophysics
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journal_title：Archives of biochemistry and biophysics
pub_type： 杂志文章
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pub_type： 杂志文章
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journal_title：Archives of biochemistry and biophysics
pub_type： 杂志文章
doi：10.1006/abbi.1993.1144
更新日期：1993-03-01 00:00:00
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journal_title：Archives of biochemistry and biophysics
pub_type： 杂志文章
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journal_title：Archives of biochemistry and biophysics
pub_type： 杂志文章
doi：10.1016/j.abb.2007.02.034
更新日期：2007-07-01 00:00:00
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journal_title：Archives of biochemistry and biophysics
pub_type： 杂志文章
doi：10.1016/j.abb.2020.108324
更新日期：2020-04-15 00:00:00
abstract：:To evaluate the conformation of reduced HEL, the monoclonal antibodies HyC1 and HyC2, which recognize different conformational epitopes on native hen egg lysozyme (HEL), were used, and the kinetics of their interactions with native HEL, S-1,2-dicarboxyethylated HEL (DCE-HEL), and carboxymethylated Cys6 and Cys127 HEL ...
journal_title：Archives of biochemistry and biophysics
pub_type： 杂志文章
doi：10.1016/j.abb.2009.11.024
更新日期：2010-02-15 00:00:00
