title: Chemical modification of proteins during peroxidation of phospholipids.
abstract: Chemical modification of proteins by advanced glycation and lipoxidation end products is implicated in the pathogenesis of macrovascular disease in aging and diabetes. To identify biomarkers of the lipoxidative modification of protein, we studied the oxidation of phospholipids in the presence of the model protein RNase A and compared protein-bound products formed in these reactions with those formed during oxidation of plasma proteins. Metal-catalyzed oxidation of 1-palmitoyl-2-arachidonoyl-phosphatidylcholine or 1-palmitoyl-2-linoleoyl-phosphatidylcholine in the presence of RNase led to the loss of amino groups in RNase and the incorporation of phosphate, hexanoate, pentanedioate, nonanedioate, and palmitate into protein. Protein-bound palmitate and phosphate correlated strongly with one another, and protein-bound pentanedioate and nonanedioate, derived from arachidonate and linoleate, respectively, accounted for approximately 20% of the cross-linking of lipid phosphorus to protein. Similar results were obtained on oxidation of total plasma or isolated LDL. We conclude that alkanedioic acids are quantitatively important linkers of oxidized phospholipids to proteins and that measurement of protein-bound phosphate and long-chain fatty acids may be useful for assessing long-term lipid peroxidative damage to proteins in vivo. Analyses of plasma proteins from control and diabetic patients indicated significant increases in lipoxidative modification of protein in diabetic compared with control subjects.
authors.affiliation: Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC 29208, USA.
authors.forename: Andrzej S
authors.initials: AS
authors.lastname: Januszewski
authors.forename: Nathan L
authors.initials: NL
authors.lastname: Alderson
authors.forename: Alicia J
authors.initials: AJ
authors.lastname: Jenkins
authors.forename: Suzanne R
authors.initials: SR
authors.lastname: Thorpe
authors.forename: John W
authors.initials: JW
authors.lastname: Baynes
mesh_terms: D000328:Adult; D001798:Blood Proteins / Q000737:chemistry*; D002384:Catalysis; D019327:Copper Sulfate / Q000737:chemistry; D003922:Diabetes Mellitus, Type 1 / Q000097:blood; D003998:Dicarboxylic Acids / Q000737:chemistry; D005260:Female; D005977:Glutarates / Q000737:chemistry; D017127:Glycation End Products, Advanced / Q000737:chemistry; D006801:Humans; D015227:Lipid Peroxidation / Q000502:physiology*; D008077:Lipoproteins, LDL / Q000737:chemistry; D008239:Lysine / Q000031:analogs & derivatives* / Q000737:chemistry; D008244:Lysophosphatidylcholines / Q000737:chemistry*; D008297:Male; D010084:Oxidation-Reduction; D010743:Phospholipids / Q000378:metabolism*; D012259:Ribonuclease, Pancreatic / Q000737:chemistry*
chemical_list: C089215:1-palmitoyl-2-lysophosphatidylcholine; D001798:Blood Proteins; D003998:Dicarboxylic Acids; D005977:Glutarates; D017127:Glycation End Products, Advanced; D008077:Lipoproteins, LDL; D008244:Lysophosphatidylcholines; D010743:Phospholipids; D012259:Ribonuclease, Pancreatic; C010038:azelaic acid; C035736:glutaric acid; D008239:Lysine; D019327:Copper Sulfate