Lipid oxidation products in cell signaling.
The recent research on the impact that oxidative changes of biolipids could have in pathophysiology serves to explain how free radical-driven reactions not only are considered as mere toxicologic events, but also modulators of cell activity and function. Oxidatively modified low-density lipoproteins are known to affect various cellular processes by modulating various molecular pathways and signaling nuclear transcription. Among the lipid oxidation products detectable in ox-LDLs, and also in the atherosclerotic plaques, 4-hydroxynonenal has been widely investigated. This aldehyde was shown to upregulate AP-1 transcription factor, signaling through the MAP kinase pathway, with eventual nuclear localization and induction of a series of genes. Further, oxidation products of cholesterol and cholesterol esters, in ox-LDL are of similar interest, especially in relation to the pathogenesis of fibrosclerotic lesions of the arterial wall.
Leonarduzzi
G
G
Department of Clinical and Biological Sciences, University of Torino, S. Luigi Gonzaga Hospital, Orbassano, Torino, Italy.
Arkan
M C
MC
Başağa
H
H
Chiarpotto
E
E
Sevanian
A
A
Poli
G
G
D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D000242:Cyclic AMP / Q000502:physiology; D004789:Enzyme Activation; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D015227:Lipid Peroxidation; D008077:Lipoproteins, LDL / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000502:physiology; D008563:Membrane Lipids / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013107:Sphingolipids / Q000502:physiology; D014158:Transcription, Genetic / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics
D000447:Aldehydes; D005231:Fatty Acids, Unsaturated; D008077:Lipoproteins, LDL; D008563:Membrane Lipids; D013107:Sphingolipids; D016212:Transforming Growth Factor beta; C099252:oxidized low density lipoprotein; D002784:Cholesterol; D000242:Cyclic AMP; D019869:Phosphatidylinositol 3-Kinases; C027576:4-hydroxy-2-nonenal