Fragmentation of DNA in P388D<sub>1</sub> macrophages exposed to oxidised low‐density lipoprotein

Reid, V.C.; Hardwick, Simon J.; Mitchinson, M. J.

doi:10.1016/0014-5793(93)80635-8

Cited by 59 publications

(25 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Indeed, oxidised LDL is known to be cytotoxic to a variety of cell types including endothelial cells, smooth muscle cells, macrophages and lymphocytes [9][10][11][12][13]. We have shown using LDL oxidised to defined extents that LDL containing the maximum level of lipid hydroperoxides (LOOH), termed moderately-oxidised LDL, can induce apoptosis in human umbilical artery smooth muscle cells, whereas native LDL does not [14].…”

Section: Introductionmentioning

confidence: 99%

Ascorbate does not protect macrophages against apoptosis induced by oxidised low density lipoprotein

Harris

Mann

Ruiz

et al. 2006

Archives of Biochemistry and Biophysics

View full text Add to dashboard Cite

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.

show abstract

Section: Introductionmentioning

confidence: 99%

Ascorbate does not protect macrophages against apoptosis induced by oxidised low density lipoprotein

Harris

Mann

Ruiz

et al. 2006

Archives of Biochemistry and Biophysics

View full text Add to dashboard Cite

show abstract

“…Quinn and co-workers have shown that oxidised LDL induces chemotaxis in human monocytes, with lysophosphatidyl choline being one of its active components [3,4]. Further, oxidised LDL has been shown to be toxic for a variety of cell types including smooth muscle cells, fibroblasts [5] and more recently mouse peritoneal macrophages [6,7], the macrophage-like cell line P388D1 [8] and human monocyte-macrophages [9]. However, oxidised LDL is a complex mixture of various components including lipid hydroperoxides, oxysterols and aldehydes [10].…”

Section: Introductionmentioning

confidence: 99%

Cytotoxic and chemotactic potencies of several aldehydic components of oxidised low density lipoprotein for human monocyte‐macrophages

et al. 1996

Self Cite

View full text Add to dashboard Cite

show abstract

“…2 Among many other effects, oxidized LDL increases the expression of cellular adhesion molecules and chemokines, 3,4 increases the production of metalloproteinases, 5 which probably destabilize the fibrous caps over advanced lesions, and induces apoptosis in cells. 6 The mechanisms by which LDL is oxidized in atherosclerotic lesions remain uncertain, despite a great deal of work. 7 The oxidation hypothesis of atherosclerosis needs to address the high antioxidant capacity of extracellular fluids.…”

mentioning

confidence: 99%

Low Density Lipoprotein Undergoes Oxidation Within Lysosomes in Cells

Wen

Leake

2007

Circulation Research

View full text Add to dashboard Cite

Abstract-The oxidized low density lipoprotein (LDL) hypothesis of atherosclerosis proposes that LDL undergoes oxidation in the interstitial fluid of the arterial wall. We have shown that aggregated (vortexed) nonoxidized LDL was taken up by J774 mouse macrophages and human monocyte-derived macrophages and oxidized intracellularly, as assessed by the microscopic detection of ceroid, an advanced lipid oxidation product. Confocal microscopy showed that the ceroid was located in the lysosomes. To confirm these findings, J774 macrophages were incubated with acetylated LDL, which is internalized rapidly to lysosomes, and then incubated (chase incubation) in the absence of any LDL. Key Words: atherosclerosis Ⅲ ceroid Ⅲ lysosome Ⅲ iron Ⅲ oxidized low density lipoprotein T he local oxidation of low density lipoprotein (LDL) within atherosclerotic lesions is widely believed to be of importance in the pathogenesis of atherosclerosis. 1 LDL is thought to be oxidized within the extracellular space of atherosclerotic lesions and then to be bound by scavenger receptors and taken up by macrophages, which become cholesterol-laden foam cells, a major feature of atherosclerotic lesions. 2 Among many other effects, oxidized LDL increases the expression of cellular adhesion molecules and chemokines, 3,4 increases the production of metalloproteinases, 5 which probably destabilize the fibrous caps over advanced lesions, and induces apoptosis in cells. 6 The mechanisms by which LDL is oxidized in atherosclerotic lesions remain uncertain, despite a great deal of work. 7 The oxidation hypothesis of atherosclerosis needs to address the high antioxidant capacity of extracellular fluids. Even a few percent of serum or interstitial fluid can inhibit greatly the oxidation of LDL by cells. 8,9 We postulated that LDL oxidation might occur not within the interstitial fluid of atherosclerotic lesions but within lysosomes in macrophages in atherosclerotic lesions. Materials and Methods LDL Isolation and ModificationBlood was taken from healthy volunteers with EDTA as the anticoagulant (final concentration 3 mmol/L). LDL (1.019 to 1.063 g/mL) was isolated from the plasma by sequential density ultracentrifugation at 4°C, as described previously. 10 LDL was stored in the dark under argon at 4°C and used within 1 month. Aggregation of LDL was achieved by vortexing 11 or acetylation. 12 Acetylation of LDL was confirmed by agarose gel electrophoresis (Paragon gels; Beckman), as seen by an increase of about 4.5 in electrophoretic mobility relative to native LDL. Cell CultureCell culture media (DMEM, RPMI 1640, and Ham's F-10) and phosphate buffered saline (PBS) (without calcium or magnesium) were obtained from Gibco Life Technologies. The media used in this study were supplemented with 20% (v/v) fetal calf serum, Glutamax (2 mmol/L), penicillin (50 IU/mL), streptomycin (50 g/mL), and amphotericin B (0.95 g/mL), unless otherwise stated. Humidified 95% air/5% carbon dioxide at 37°C was used for cell culture. J774 cells were regularly cultured in supplement...

show abstract

Fragmentation of DNA in P388D₁ macrophages exposed to oxidised low‐density lipoprotein

Cited by 59 publications

References 21 publications

Ascorbate does not protect macrophages against apoptosis induced by oxidised low density lipoprotein

Ascorbate does not protect macrophages against apoptosis induced by oxidised low density lipoprotein

Cytotoxic and chemotactic potencies of several aldehydic components of oxidised low density lipoprotein for human monocyte‐macrophages

Low Density Lipoprotein Undergoes Oxidation Within Lysosomes in Cells

Contact Info

Product

Resources

About

Fragmentation of DNA in P388D1 macrophages exposed to oxidised low‐density lipoprotein

Cited by 59 publications

References 21 publications

Ascorbate does not protect macrophages against apoptosis induced by oxidised low density lipoprotein

Ascorbate does not protect macrophages against apoptosis induced by oxidised low density lipoprotein

Cytotoxic and chemotactic potencies of several aldehydic components of oxidised low density lipoprotein for human monocyte‐macrophages

Low Density Lipoprotein Undergoes Oxidation Within Lysosomes in Cells

Contact Info

Product

Resources

About

Fragmentation of DNA in P388D₁ macrophages exposed to oxidised low‐density lipoprotein