Ascorbate does not protect macrophages against apoptosis induced by oxidised low density lipoprotein.
Apoptosis of macrophages and smooth muscle cells is observed in atherosclerotic lesions and may play an important role in the disease progression. Oxidised low density lipoprotein (LDL) is cytotoxic and induces apoptosis in a variety of cell types. We reported previously that ascorbate protects arterial smooth muscle cells from apoptosis induced by oxidised LDL containing the peak levels of lipid hydroperoxides. We now demonstrate that macrophages undergo apoptosis when treated with this species of oxidised LDL, as detected by increased annexin V binding and DNA fragmentation. Ascorbate treatment of macrophages did not protect against the cytotoxicity of oxidised LDL, and modestly increased the levels of annexin V binding and DNA fragmentation. Oxidised LDL treatment also increased the expression of the antioxidant stress protein heme oxygenase-1 in macrophages; however, this increase was markedly attenuated by ascorbate pretreatment. Although apoptosis induced by oxidised LDL was modestly promoted by ascorbate, ascorbate apparently decreased the levels of oxidative stress in macrophages, suggesting that this pro-apoptotic effect was not mediated by a pro-oxidant mechanism, but may instead have been due to intracellular protection of the apoptotic machinery by ascorbate.
Harris
Lynda K
LK
Cell and Molecular Biology Research Division, School of Biological Sciences, The University of Reading, Whiteknights, P.O. Box 228, Reading, Berkshire RG6 6AJ, UK.
Mann
Giovanni E
GE
Ruiz
Emilio
E
Mushtaq
Sohail
S
Leake
David S
DS
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001205:Ascorbic Acid / Q000378:metabolism / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005227:Fatty Acids / Q000032:analysis; D005434:Flow Cytometry; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000378:metabolism; D013997:Time Factors
D005227:Fatty Acids; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D010088:Oxidoreductases; D051547:Heme Oxygenase-1; D001205:Ascorbic Acid