Covalent binding of hydroxy-alkenals 4-HDDE, 4-HHE, and 4-HNE to ethanolamine phospholipid subclasses.
Lipid oxidation is implicated in a wide range of pathophysiogical disorders, and leads to reactive compounds such as fatty aldehydes, of which the most well known is 4-hydroxy-2E-nonenal (4-HNE) issued from 15-hydroperoxyeicosatetraenoic acid (15-HpETE), an arachidonic acid (AA) product. In addition to 15-HpETE, 12(S)-HpETE is synthesized by 12-lipoxygenation of platelet AA. We first show that 12-HpETE can be degraded in vitro into 4-hydroxydodeca-(2E,6Z)-dienal (4-HDDE), a specific aldehyde homologous to 4-HNE. Moreover, 4-HDDE can be detected in human plasma. Second, we compare the ability of 4-HNE, 4-HDDE, and 4-hydroxy-2E-hexenal (4-HHE) from n-3 fatty acids to covalently modify different ethanolamine phospholipids (PEs) chosen for their biological relevance, namely AA- (20: 4n-6) or docosahexaenoic acid- (22:6n-3) containing diacyl-glycerophosphoethanolamine (diacyl-GPE) and alkenylacyl-glycerophosphoethanolamine (alkenylacyl-GPE) molecular species. The most hydrophobic aldehyde used, 4-HDDE, generates more adducts with the PE subclasses than does 4-HNE, which itself appears more reactive than 4-HHE. Moreover, the aldehydes show higher reactivity toward alkenylacyl-GPE compared with diacyl-GPE, because the docosahexaenoyl-containing species are more reactive than those containing arachidonoyl. We conclude that the different PE species are differently targeted by fatty aldehydes: the higher their hydrophobicity, the higher the amount of adducts made. In addition to their antioxidant potential, alkenylacyl-GPEs may efficiently scavenge fatty aldehydes.
Bacot
Sandrine
S
Physiologie des lipides et membranes, INSERM U585, France.
Bernoud-Hubac
Nathalie
N
Baddas
Naima
N
Chantegrel
Bernard
B
Deshayes
Christian
C
Doutheau
Alain
A
Lagarde
Michel
M
Guichardant
Michel
M
D000447:Aldehydes / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D015118:Eicosapentaenoic Acid / Q000737:chemistry; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D010714:Phosphatidylethanolamines / Q000737:chemistry* / Q000378:metabolism; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D013997:Time Factors
C480745:4-hydroxydodeca-2,6-dienal; D000447:Aldehydes; D010714:Phosphatidylethanolamines; D010743:Phospholipids; C045934:4-hydroxy-2-hexenal; D015118:Eicosapentaenoic Acid; C027576:4-hydroxy-2-nonenal