Document Detail


Formation of a vitamin C conjugate of acrolein and its paraoxonase-mediated conversion into 5,6,7,8-tetrahydroxy-4-oxooctanal.
MedLine Citation:
PMID:  20353174     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Vitamin C (ascorbic acid) has been reported to participate in Michael addition reactions in vitro to form vitamin C conjugates with alpha,beta-unsaturated aldehydes, such as acrolein. This study shows evidence for the formation and metabolism of the vitamin C conjugate of acrolein (AscACR) in cultured human monocytic THP-1 cells exposed to acrolein diacetate. By using (18)O and (13)C labeling in combination with liquid chromatography-tandem mass spectrometry, AscACR was shown to undergo hydrolytic conversion of the ascorbyl lactone into an intermediate carboxylic acid. Subsequent decarboxylation of the carboxylic acid yielded 5,6,7,8-tetrahydroxy-4-oxooctanal (THO). When THP-1 cells were pretreated with ascorbic acid (1 mM, 18 h) and then exposed to acrolein diacetate, THO was detected as its pentafluorobenzyl oxime derivative in the cell lysates and medium. Treatment of THP-1 cells with both ascorbic acid and acrolein diacetate was required for THO formation. The formation of THO from AscACR was facilitated by the lactonase enzymes, human recombinant paraoxonases 1 and 2. THP-1 cells exhibited PON activity, which explains the catalytic conversion of AscACR into THO in these cells. THO was formed in addition to metabolites of the glutathione conjugate of acrolein, indicating that THO formation contributes to the elimination of acrolein in a cellular environment.
Authors:
Nicholas G Kesinger; Brandi L Langsdorf; Alexandre F Yokochi; Cristobal L Miranda; Jan F Stevens
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Chemical research in toxicology     Volume:  23     ISSN:  1520-5010     ISO Abbreviation:  Chem. Res. Toxicol.     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-04-19     Completed Date:  2010-07-27     Revised Date:  2011-09-26    
Medline Journal Info:
Nlm Unique ID:  8807448     Medline TA:  Chem Res Toxicol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  836-44     Citation Subset:  IM    
Affiliation:
Linus Pauling Institute, and the Department of Pharmaceutical Sciences, Oregon State University, Corvallis, Oregon 97331, USA.
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MeSH Terms
Descriptor/Qualifier:
Acrolein / chemistry,  metabolism*,  toxicity
Aryldialkylphosphatase / genetics,  metabolism*
Ascorbic Acid / chemistry,  pharmacology*
Cell Line
Chromatography, High Pressure Liquid
Humans
Isotope Labeling
Monosaccharides / biosynthesis,  chemistry,  metabolism*
Recombinant Proteins / genetics,  metabolism
Spectrometry, Mass, Electrospray Ionization
Grant Support
ID/Acronym/Agency:
P30 ES000210/ES/NIEHS NIH HHS; P30 ES000210-41/ES/NIEHS NIH HHS; R01 HL081721-04/HL/NHLBI NIH HHS; R01HL081721/HL/NHLBI NIH HHS; S10 RR022589/RR/NCRR NIH HHS; S10 RR022589-010001/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/5,6,7,8-tetrahydroxy-4-oxooctanal; 0/Monosaccharides; 0/Recombinant Proteins; 107-02-8/Acrolein; 50-81-7/Ascorbic Acid; EC 3.1.8.1/Aryldialkylphosphatase
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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