Caspase-Dependent Apoptosis in THP-1 Cells Exposed to Oxidized Low-Density Lipoproteins

Vicca, Stéphanie; Hennequin, Carole; Nguyen–Khoa, Thao; Massy, Ziad A.; Descamps‐Latscha, Béatrice; Drüeke, Tilman B.; Lacour, Bernard

doi:10.1006/bbrc.2000.3017

Cited by 44 publications

(30 citation statements)

References 34 publications

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“…For example, recent evidence suggests that oxidized LDL induces apoptosis both through activation of death receptors and through mitochondrial pathways. It has also recently been reported that the oxysterols, lipid hydroperoxides, oxidized phospholipids, and free cholesterol found within oxidized LDL independently induce death (2,5,11,27,28,30,36,47,50,51,(53)(54)(55). In the present study and in keeping with previous observations, it was found that even very low concentrations of oxidized LDL were capable of inducing markers of apoptosis in the RAW cells, C. pneumoniae is an obligate intracellular pathogen, and as such this organism is dependent on the continued functioning of the host cell to support bacterial growth and the capacity for sustained infection.…”

Section: Discussionmentioning

confidence: 97%

“…Most macrophages within atherosclerotic plaques are converted into foam cells by the unregulated accumulation of lipid. Components of oxidized low-density lipoprotein (ox-LDL) and/or unesterified cholesterol kill cultured macrophages by both apoptotic and nonapoptotic pathways (2,5,11,27,28,30,36,47,50,51,(53)(54)(55). To date, it is not known whether C. pneumoniae infection kills macrophage-derived foam cells and, in turn, contributes to the destabilization of advanced atherosclerotic lesions.…”

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confidence: 99%

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Chlamydia pneumoniaeAugments the Oxidized Low-Density Lipoprotein-Induced Death of Mouse Macrophages by a Caspase-Independent Pathway

Yaraei¹,

Campbell²,

Zhu

et al. 2005

Infect Immun

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Chlamydia pneumoniae is a common respiratory pathogen that is associated with an increased risk of cardiovascular disease. However, the mechanisms by which C. pneumoniae contributes to cardiovascular disease have not been determined yet. C. pneumoniae infection may accelerate the death of cells within atherosclerotic lesions and contribute to the formation of unstable lesions. To test this hypothesis, the impact of C. pneumoniae infection on the death of lipid-loaded mouse macrophages was investigated. It was observed that RAW 264.7 cells are highly susceptible to the toxic effects of oxidized low-density lipoprotein (LDL) and exhibit markers of cell death within 24 h of treatment with as little as 5 g/ml oxidized LDL. Subsequent infection with either live C. pneumoniae or heat-killed or UV-inactivated C. pneumoniae at a low multiplicity of infection for 24 to 72 h stimulated both additional binding of annexin V and the uptake of propidium iodide. Thus, C. pneumoniae augments the effects of oxidized LDL on cell death independent of a sustained infection. However, unlike oxidized LDL, C. pneumoniae infection does not activate caspase 3 or induce formation of the mitochondrial transition pore or the fragmentation of DNA, all of which are classical markers of apoptosis. Furthermore, primary bone marrow macrophages isolated from mice deficient in Toll-like receptor 2 (TLR-2) but not TLR-4 are resistant to C. pneumoniae-induced death. These data suggest that C. pneumoniae kills cells by a caspase-independent pathway and that the process is potentially mediated by activation of TLR-2.

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Section: Discussionmentioning

confidence: 97%

mentioning

confidence: 99%

Chlamydia pneumoniaeAugments the Oxidized Low-Density Lipoprotein-Induced Death of Mouse Macrophages by a Caspase-Independent Pathway

Yaraei¹,

Campbell²,

Zhu

et al. 2005

Infect Immun

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“…LDL (Density=1.020-1.063 g/ml) was isolated by sequential flotation ultracentrifugation from human plasma as previously described (21). Hypochlorite modification of LDL was essentially performed according to Vicca et al (22). Ox-LDL was dialyzed overnight against 10 mM phosphate-buffered saline (PBS) (pH 7.4).…”

Section: Methodsmentioning

confidence: 99%

Identification of lipid droplet-associated proteins in the formation of macrophage-derived foam cells using microarrays

Song²,

Li³

et al. 2010

Int J Mol Med

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Abstract.A large number of macrophage-derived foam cells stores excessive neutral lipids in intracellular droplets, and plays a major role during the development of atherosclerosis. The formation and catabolism of intracellular lipid droplets (LDs) are regulated by LD-associated proteins, a group of proteins which are located on the surface of LDs and regulate the formation, morphology and lipolysis of LDs. In order to illustrate the function of LD-associated proteins during the process of atherosclerosis, the foam cell model is induced by oxidized low-density lipoprotein (ox-LDL) in macrophages originated from the THP-1 cell line, and cDNA microarrays are used to monitor the gene expression profiles of LD-associated proteins. Gene expression data show that 2% of changed genes are lipid binding genes during the transformation of foam cells. The major candidate genes, the cell deathinducing DFF45-like effector (CIDE) family and Perilipin, Adipophilin, and TIP47 (PAT) family, have different alterations during the formation of foam cells. CIDEB, CIDEC, Adipophilin, S3-12 and LSDP5 were up-regulated, while TIP47 was down-regulated. There was no significant change in CIDEA and Perilipin. These results were confirmed by real-time PCR and immunoblotting. This study presents a comprehensive analysis of the gene expression of LDassociated proteins during the differentiation of human foam cells, which may play an important role in the process of atherosclerosis.

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“…Apoptosis Assay-THP-1 cells were incubated with increasing concentrations of oxLDL for 24 and 48 h and then stained with Hoechst 33342 (5 g/ml) for 1 h at 37°C (58). A total of 200 cells for each treatment were counted, and the percentage of apoptotic cells with condensed nuclei was quantified.…”

Section: Methodsmentioning

confidence: 99%

Antagonistic Effects of Oxidized Low Density Lipoprotein and α-Tocopherol on CD36 Scavenger Receptor Expression in Monocytes

Munteanu

Taddei

Tamburini

et al. 2006

Journal of Biological Chemistry

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Vitamin E deficiency increases expression of the CD36 scavenger receptor, suggesting specific molecular mechanisms and signaling pathways modulated by ␣-tocopherol. We show here that ␣-tocopherol down-regulated CD36 expression (mRNA and protein) in oxidized low density lipoprotein (oxLDL)-stimulated THP-1 monocytes, but not in unstimulated cells. Furthermore, ␣-tocopherol treatment of monocytes led to reduction of fluorescent oxLDL-3,3-dioctadecyloxacarbocyanine perchlorate binding and uptake. Protein kinase C (PKC) appears not to be involved because neither activation of PKC by phorbol 12-myristate 13-acetate nor inhibition by PKC412 was affected by ␣-tocopherol. However, ␣-tocopherol could partially prevent CD36 induction after stimulation with a specific agonist of peroxisome proliferator-activated receptor-␥ (PPAR␥; troglitazone), indicating that this pathway is susceptible to ␣-tocopherol action. Phosphorylation of protein kinase B (PKB) at Ser 473 was increased by oxLDL, and ␣-tocopherol could prevent this event. Expression of PKB stimulated the CD36 promoter as well as a PPAR␥ element-driven reporter gene, whereas an inactive PKB mutant had no effect. Moreover, coexpression of PPAR␥ and PKB led to additive induction of CD36 expression. Altogether, our results support the existence of PKB/PPAR␥ signaling pathways that mediate CD36 expression in response to oxLDL. The activation of CD36 expression by PKB suggests that both lipid biosynthesis and fatty acid uptake are stimulated by PKB.In many cell types, oxidized low density lipoproteins (oxLDL) 2 modulate cellular processes such as apoptosis, adhesion, migration, gene expression, and the induction of signal transduction cascades (1). Exposure of monocytes to oxLDL may alter gene expression and signaling, making them more susceptible to the following pro-atherogenic stimuli. The migration of monocytes into the intima and the conversion of monocytes/macrophages into foam cells represent initial steps in atherosclerosis. Current strategies to prevent atherosclerosis are aimed either at lowering the cholesterol load of lipoproteins or at reducing oxidative stress.Vitamin E is a redox-active natural compound that can act, depending on the conditions, as a pro-or antioxidant on low density lipoproteins (LDL) in vitro and in vivo (2-5). The major form of vitamin E in human plasma is ␣-tocopherol, and reduced plasma levels of ␣-tocopherol, such as in vitamin E-deficient mice, increase the incidence of atherosclerosis (6). Animal and cell culture studies strongly suggest that vitamin E can prevent atherosclerosis; however, the anti-atherogenic effects in clinical trials are still controversial (7-10). ␣-Tocopherol in lipoproteins (mainly LDL) and also in the subendothelial space has been assumed to play a central role in reducing atherosclerosis by preventing lipid peroxidation and consequent lesion development. Nevertheless, since many compounds exist that can interfere with the oxidation of LDL without being equally effective, alternative modes of action have bee...

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Caspase-Dependent Apoptosis in THP-1 Cells Exposed to Oxidized Low-Density Lipoproteins

Cited by 44 publications

References 34 publications

Chlamydia pneumoniaeAugments the Oxidized Low-Density Lipoprotein-Induced Death of Mouse Macrophages by a Caspase-Independent Pathway

Chlamydia pneumoniaeAugments the Oxidized Low-Density Lipoprotein-Induced Death of Mouse Macrophages by a Caspase-Independent Pathway

Identification of lipid droplet-associated proteins in the formation of macrophage-derived foam cells using microarrays

Antagonistic Effects of Oxidized Low Density Lipoprotein and α-Tocopherol on CD36 Scavenger Receptor Expression in Monocytes

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