| Pyridoxamine analogues scavenge lipid-derived gamma-ketoaldehydes and protect against H2O2-mediated cytotoxicity. | |
| | |
MedLine Citation:
|
PMID: 17176098 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Isoketals and levuglandins are highly reactive gamma-ketoaldehydes formed by oxygenation of arachidonic acid in settings of oxidative injury and cyclooxygenase activation, respectively. These compounds rapidly adduct to proteins via lysyl residues, which can alter protein structure/function. We examined whether pyridoxamine, which has been shown to scavenge alpha-ketoaldehydes formed by carbohydrate or lipid peroxidation, could also effectively protect proteins from the more reactive gamma-ketoaldehydes. Pyridoxamine prevented adduction of ovalbumin and also prevented inhibition of RNase A and glutathione reductase activity by the synthetic gamma-ketoaldehyde, 15-E2-isoketal. We identified the major products of the reaction of pyridoxamine with the 15-E2-isoketal, including a stable lactam adduct. Two lipophilic analogues of pyridoxamine, salicylamine and 5'-O-pentylpyridoxamine, also formed lactam adducts when reacted with 15-E2-isoketal. When we oxidized arachidonic acid in the presence of pyridoxamine or its analogues, pyridoxamine-isoketal adducts were found in significantly greater abundance than the pyridoxamine-N-acyl adducts formed by alpha-ketoaldehyde scavenging. Therefore, pyridoxamine and its analogues appear to preferentially scavenge gamma-ketoaldehydes. Both pyridoxamine and its lipophilic analogues inhibited the formation of lysyl-levuglandin adducts in platelets activated ex vivo with arachidonic acid. The two lipophilic pyridoxamine analogues provided significant protection against H2O2-mediated cytotoxicity in HepG2 cells. These results demonstrate the utility of pyridoxamine and lipophilic pyridoxamine analogues to assess the potential contributions of isoketals and levuglandins in oxidant injury and inflammation and suggest their potential utility as pharmaceutical agents in these conditions. |
| | |
Authors:
|
Sean S Davies; Eric J Brantley; Paul A Voziyan; Venkataraman Amarnath; Irene Zagol-Ikapitte; Olivier Boutaud; Billy G Hudson; John A Oates; L Jackson Roberts |
Related Documents
:
|
15801778 - Treatment of germinated wheat to increase levels of gaba and ip6 catalyzed by endogenou... 3873258 - Incorporation of chorismic acid and 4-aminobenzoic acid into the 4-hydroxyaniline moiet... 7452248 - The gamma-aminobutyrate content of nerve endings (synaptosomes) in mice after the intra... 8937438 - Biological properties of fluoroglutamate-containing analogs of folates and methotrexate... 16209608 - An efficient synthesis of a dual ppar alpha/gamma agonist and the formation of a steric... 11729118 - Duodenal reflux induces cyclooxygenase-2 in the esophageal mucosa of rats: evidence for... |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2006-12-06 |
Journal Detail:
|
Title: Biochemistry Volume: 45 ISSN: 1520-4995 ISO Abbreviation: Biochemistry Publication Date: 2006 Dec |
Date Detail:
|
Created Date: 2007-03-06 Completed Date: 2008-01-11 Revised Date: 2011-09-26 |
Medline Journal Info:
|
Nlm Unique ID: 0370623 Medline TA: Biochemistry Country: United States |
Other Details:
|
Languages: eng Pagination: 15756-67 Citation Subset: IM |
Affiliation:
|
Departments of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232, USA. sean.davies@vanderbilt.edu |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Aldehydes
/
chemistry,
metabolism* Animals Arachidonic Acids / chemistry, metabolism Catalysis Cell Line, Tumor Free Radical Scavengers / chemistry, metabolism Humans Hydrogen Peroxide / antagonists & inhibitors, chemistry, toxicity* Isoprostanes / chemistry, metabolism Lipids / chemistry* Ovalbumin / chemistry, metabolism Prostaglandins E / chemistry, metabolism Pyridoxamine / analogs & derivatives*, chemistry*, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
|
AG26119/AG/NIA NIH HHS; DK065138/DK/NIDDK NIH HHS; DK20593/DK/NIDDK NIH HHS; DK26657/DK/NIDDK NIH HHS; GM15431/GM/NIGMS NIH HHS; GM42056/GM/NIGMS NIH HHS; P30 DK026657-25/DK/NIDDK NIH HHS; P50 GM015431-40/GM/NIGMS NIH HHS; P60 DK020593-190004/DK/NIDDK NIH HHS; R01 DK065138-06/DK/NIDDK NIH HHS; R21 AG026119-02/AG/NIA NIH HHS; R37 GM042056-20/GM/NIGMS NIH HHS; T35 DK007383-19/DK/NIDDK NIH HHS; T35-DK07383/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Aldehydes; 0/Arachidonic Acids; 0/Free Radical Scavengers; 0/Isoprostanes; 0/Lipids; 0/Prostaglandins E; 7722-84-1/Hydrogen Peroxide; 85-87-0/Pyridoxamine; 9006-59-1/Ovalbumin; 91712-41-3/levuglandin E2 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: An optical signal correlated with the allosteric transition in Scapharca inaequivalvis HbI.
Next Document: Effect of cholesterol on the interaction of the HIV GP41 fusion peptide with model membranes. Import...