Oxidized low-density lipoprotein-induced apoptosis.
Cultured cells are able to oxidize low-density lipoproteins (LDL) and oxidized LDL (oxLDL), which are present in atherosclerosis areas, exhibit a variety of biological properties potentially involved in atherogenesis. This review is focused on the toxicity of oxLDL, more precisely on the toxic compounds generated during LDL oxidation, the features and the mechanisms of cell death (apoptosis or necrosis) induced by oxLDL. After internalization, toxic oxidized lipids, namely lipid peroxides, oxysterols and aldehydes, induce modifications of cell proteins, elicit oxidative stress, lipid peroxidation and alter various signaling pathways and gene expression. These events may participate in the toxic effect, and converge to trigger an intense, delayed and sustained calcium peak which elicits either apoptosis or necrosis processes. OxLDL-induced apoptosis involves both mitochondrial and death-receptor (Fas/FasL) apoptotic pathways, thereby activating the classical caspase cascade and subsequent biochemical and morphological apoptotic features. When apoptosis is blocked by overexpression of Bcl-2, oxLDL trigger necrosis through a calcium-dependent pathway. Apoptosis occurring in atherosclerotic areas is potentially involved in endothelial cell lining defects, necrotic core formation and plaque rupture or erosion which may trigger atherothrombotic events. However, the precise role of oxLDL in apoptosis/necrosis occurring in vivo in atherosclerotic plaques remains to be clarified.
Salvayre
Robert
R
INSERM U-466, Faculty of Medicine, University Paul Sabatier, CHU Rangueil, Avenue Jean Poulhès, 31054 Toulouse cedex 04, France. salvayre@toulouse.inserm.fr
Auge
Nathalie
N
Benoist
Herve
H
Negre-Salvayre
Anne
A
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001161:Arteriosclerosis / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D053222:Fas Ligand Protein; D006801:Humans; D015227:Lipid Peroxidation; D008054:Lipid Peroxides / Q000633:toxicity; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000502:physiology* / Q000633:toxicity; D008246:Lysophospholipids / Q000737:chemistry / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D009336:Necrosis; D010084:Oxidation-Reduction; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D013107:Sphingolipids / Q000737:chemistry / Q000378:metabolism
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008054:Lipid Peroxides; D008077:Lipoproteins, LDL; D008246:Lysophospholipids; D008562:Membrane Glycoproteins; D010743:Phospholipids; D017382:Reactive Oxygen Species; D013107:Sphingolipids; C099252:oxidized low density lipoprotein; D020169:Caspases