Covalent binding of isoketals to ethanolamine phospholipids.
Free radicals have been strongly implicated in the pathogenesis of many human diseases. We previously identified the formation of highly reactive gamma-ketoaldehydes, isoketals, in vivo as products of free radical-induced peroxidation of arachidonic acid. Isoketals react with lysine residues on proteins at a rate that far exceeds that of 4-hydroxynonenal and demonstrate a unique proclivity to crosslink proteins. Hydroxynonenal has been shown to react with aminophospholipids, particularly phosphatidylethanolamine. We explored whether isoketals also react with phosphatidylethanolamine. Using liquid chromatography/electrospray mass spectrometry, we found that isoketals form pyrrole and Schiff base adducts with phosphatidylethanolamine. In addition, the ability of isoketals to covalently modify phosphatidylethanolamine is greater than that of 4-hydroxynonenal. These studies identify in vitro novel isoketal adducts. This provides the basis to explore the formation of isoketal-aminophospholipid adducts in vivo and the biological consequences of the formation of these adducts.
Bernoud-Hubac
Nathalie
N
INSERM U585, Physiopathologie des Lipides et Membranes, INSA-Lyon, 69621 Villeurbanne, France. Nathalie.Bernoud-Hubac@insa-lyon.fr
Fay
Laurent B
LB
Armarnath
Venkataraman
V
Guichardant
Michel
M
Bacot
Sandrine
S
Davies
Sean S
SS
Roberts
L Jackson
LJ
Lagarde
Michel
M
D000447:Aldehydes / Q000737:chemistry; D016718:Arachidonic Acid / Q000737:chemistry*; D002853:Chromatography, Liquid; D003432:Cross-Linking Reagents / Q000737:chemistry*; D005609:Free Radicals / Q000737:chemistry*; D013058:Mass Spectrometry; D010714:Phosphatidylethanolamines / Q000737:chemistry*; D012545:Schiff Bases / Q000737:chemistry
D000447:Aldehydes; D003432:Cross-Linking Reagents; D005609:Free Radicals; D010714:Phosphatidylethanolamines; D012545:Schiff Bases; D016718:Arachidonic Acid; C483858:phosphatidylethanolamine; C027576:4-hydroxy-2-nonenal