Abstract：
:Treatment of hepatic microsomes with Fe(3+)/ascorbate activates UDP-glucuronyltransferase (UGT), a phenomenon totally prevented and reversed by reducing agents. At microM concentrations, iron and copper ions catalyze the formation of ROS through Fenton and/or Haber-Weiss reactions. Unlike iron ions, indiscriminate binding of copper ions to thiol groups of proteins different from the specialized copper-binding proteins may occur. Thus, we hypothesize that incubation of hepatic microsomes with the Cu(2+)/ascorbate system will lead to both UGT oxidative activation and Cu(2+)-binding induced inhibition, simultaneously. We studied the effects of Cu(2+) alone and in the presence of ascorbate on rat liver microsomal UGT activity. Our results show that the effects of both copper alone and in the presence of ascorbate were copper ion concentration- and incubation time-dependent. At very low Cu(2+) (25nM), this ion did not modify UGT activity. In the presence of ascorbate, however, UGT activity was increased. At higher copper concentrations (10 and 50microM), this ion led to UGT activity inhibition. In the presence of ascorbate, 10microM Cu(2+) activated UGT at short incubation periods but inhibited this enzyme at longer incubation times; 50microM Cu(2+) only inhibited UGT activity. Thiol reducing agent 2,4-dithiothreitol prevented and reversed UGT activation while EDTA prevented both, UGT activation and inhibition. Our results are consistent with a model in which Cu(2+)-induced oxidation of UGT leads to the activation of the enzyme, while Cu(2+)-binding leads to its inhibition. We discuss physiological and pathological implications of these findings.
journal_name
Chem Biol Interactjournal_title
Chemico-biological interactionsauthors
Letelier ME,Lagos F,Faúndez M,Miranda D,Montoya M,Aracena-Parks P,González-Lira Vdoi
10.1016/j.cbi.2006.12.010subject
Has Abstractpub_date
2007-04-05 00:00:00pages
1-11issue
1eissn
0009-2797issn
1872-7786pii
S0009-2797(06)00363-2journal_volume
167pub_type
杂志文章abstract：:Numerous reactive oxygen species (ROS) and reactive carbonyl species (RCS) issuing from lipid and sugar oxidation are known to damage a large number of proteins leading to enzyme inhibition and alteration of cellular functions. Whereas studies in literature only focus on the reactivity of one or two of these compounds...
journal_title：Chemico-biological interactions
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journal_title：Chemico-biological interactions
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journal_title：Chemico-biological interactions
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journal_title：Chemico-biological interactions
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pub_type： 杂志文章,评审
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更新日期：2020-12-01 00:00:00
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journal_title：Chemico-biological interactions
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journal_title：Chemico-biological interactions
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pub_type： 杂志文章
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journal_title：Chemico-biological interactions
pub_type： 杂志文章,评审
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
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更新日期：2018-04-01 00:00:00
