Glutathione (GSH) and the toxicity of oxidised low-density lipoprotein to human monocyte-macrophages.
Macrophage death, believed to be an important event in the pathogenesis of human atherosclerosis, can be induced by oxidised low-density lipoprotein (LDL) in vitro. Supplementation of the culture medium with 5 mM GSH significantly protected human monocyte-macrophages in vitro against the toxicity of copper-oxidised LDL. Oxidation products of LDL include the aldehyde 4-hydroxynonenal (HNE). We present evidence that conjugation of HNE by GSH contributes to this protection. In the absence of cells, HPLC analysis showed there were marked reductions in the levels of both pure HNE and HNE in copper-oxidised LDL in the presence of GSH. However, GSH did not reverse protein modification, as judged by agarose gel electrophoresis, nor did it influence the depletion of polyunsaturated fatty acids, which were assessed using gas chromatography. The possible implications for human atherosclerosis are discussed.
Hardwick
S J
SJ
University of Cambridge, Department of Pathology, UK. sjh@mole.bio.cam.ac.uk
Carpenter
K L
KL
Allen
E A
EA
Mitchinson
M J
MJ
D000447:Aldehydes / Q000378:metabolism / Q000494:pharmacology; D016718:Arachidonic Acid / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003300:Copper / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004586:Electrophoresis; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D005978:Glutathione / Q000494:pharmacology*; D006801:Humans; D006888:Hydroxycholesterols / Q000378:metabolism; D019787:Linoleic Acid / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000633:toxicity; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016877:Oxidants / Q000378:metabolism; D010084:Oxidation-Reduction
D000447:Aldehydes; D005231:Fatty Acids, Unsaturated; D006888:Hydroxycholesterols; D008077:Lipoproteins, LDL; D016877:Oxidants; C099252:oxidized low density lipoprotein; D016718:Arachidonic Acid; C011724:cholest-5-en-3 beta,7 alpha-diol; D003300:Copper; D019787:Linoleic Acid; D005978:Glutathione; C027576:4-hydroxy-2-nonenal