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.
Department of Clinical and Biological Sciences, University of Torino, S. Luigi Gonzaga Hospital, Orbassano, Torino, Italy.
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Leonarduzzi
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Arkan
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Başağa
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Chiarpotto
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Sevanian
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Poli
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