5-Lipoxygenase is not essential in macrophage-mediated oxidation of low-density lipoprotein

Jessup, Wendy; Darley‐Usmar, Victor; O'leary, Vanessa J.; Bedwell, Stephen

doi:10.1042/bj2780163

Cited by 66 publications

(21 citation statements)

References 22 publications

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“…According to the latter study, 5-LO is the main lipoxygenase expressed within atherosclerotic lesions [33]. Since the role of 5-LO in LDL oxidations appears less convincing compared with the actions of 15-LO [34,35], the atherogenic role of 5-LO may rather be dependent on its participation in the biosynthesis of LTs, and the pro-inflammatory signaling transduced through LT receptor activation [29]. The latter notion is supported by findings in atherosclerotic apolipo- Fig.…”

Section: Lipid Retention and Modificationsupporting

confidence: 63%

Leukotriene Signaling in Atherosclerosis and Ischemia

Bäck

2008

Cardiovasc Drugs Ther

118

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Section: Lipid Retention and Modificationsupporting

confidence: 63%

Leukotriene Signaling in Atherosclerosis and Ischemia

Bäck

2008

Cardiovasc Drugs Ther

118

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“…Native LDL does not cause foam cell formation because accumulation of cholesteryl esters is prevented by a sterol dependent down-regulation of the native LDL receptor [3]. LDL can be modified so that is recognized by the macrophage scavenger receptor by any of the following means: acetylation [5], acetoacetylation [6], malondialdehyde (MDA) treatment [7], hypochlorite treatment [S] and oxidation, either by copper [9] or by cells such as endothelial cells [IO,111, smooth muscle cells [12], platelets [13] and monocytes/macrophages [14,15]. LDL may also be modified by treatment with phospholipase C [16] or lipoxygenase plus phospholipase A, [17], and by haem proteins [18].…”

Section: Introductionmentioning

confidence: 99%

Peroxynitrite modification of low‐density lipoprotein leads to recognition by the macrophage scavenger receptor

et al. 1993

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Peroxynitrite is an oxidant which could be formed in the vasculature by the reaction of superoxide with nitric oxide. It is capable of modifying amino acid residues and of initiating lipid peroxidation. In the present study we have shown that peroxynitrite converts low density lipoprotein to a form recognized by the macrophage scavenger receptor and that this process is associated with modification of the protein and lipid, and with the oxidation of a-tocopherol to a-tocopherol quinone.

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“…I-LDL Degradation-Iodination of LDL was performed with Na 125 I as described by the iodine monochloride method (38), and the iodinated LDL (specific radioactivity 60 cpm/ng of LDL protein) was separated from unreacted iodide using a column of Sephadex G-25 (PD-10, Pharmacia Biotech, Inc.) followed by dialysis overnight against PBS at 4°C. Macrophage-modified LDL (24 h incubation) was incubated in degradation assays as described (39).…”

mentioning

confidence: 99%

Disruption of 12/15-Lipoxygenase Expression in Peritoneal Macrophages

Sun

Funk

1996

Journal of Biological Chemistry

233

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By in situ hybridization we show that the L-12LO gene is expressed abundantly in a subset of peritoneal macrophages but not in elicited leukocytes, alveolar macrophages, or bone marrow-derived macrophages. L-12LO is highly related to human and rabbit 15-lipoxygenases, enzymes that have been implicated in the maturation process of red blood cells, and the oxidative modification of low density lipoproteins that is implicated in atherogenesis. Accordingly, these enzymes have been referred to as 12/15-lipoxygenases. We have inactivated the L-12LO gene in mice using homologous recombination in embryonic stem cells. Macrophage expression of L-12LO was abolished in homozygous deficient mice as was formation of 12-hydroxyeicosatetraenoic acid (12-HETE). In zymosan-stimulated cells, there was significant diversion of metabolism to the 5-lipoxygenase products leukotriene C 4 and 5-HETE and in A23187-treated cells to 5-HETE only. The enhanced formation of 5-lipoxygenase metabolites was not due to compensatory changes of 5-lipoxygenase or 5-lipoxygenase activating protein but rather an apparent substrate diversion. L-12LO-deficient mice have no obvious abnormalities in reticulocyte or mature red blood cells, which suggest that in mice this pathway is not functionally important for erythrocytic development. Indices for oxidation of low density lipoprotein (measured as either thiobarbituric acid-reactive substances or the oxidant stress marker isoprostane 8-epi-prostaglandin F 2␣ ) were identical in incubations with unstimulated wild-type and L-12LO-deficient macrophages, but the zymosan-induced increase observed with wild-type macrophages was abolished in L-12LO-deficient cells. Thus, 12/15-lipoxygenase-deficient mice will be useful for the study of interaction between lipoxygenase pathways and determination of the in vivo role of 12/15-lipoxygenase-catalyzed oxidation of LDL in atherogenesis.12-Lipoxygenase incorporates stereospecifically molecular oxygen into arachidonic acid to form 12-hydroperoxyeicosatetraenoic acid (12-HPETE).1 Two types of 12-lipoxygenase enzymes have been described that differ biochemically and in immunoreactivity (1, 2). The primary sequences are 58 -65% identical based on the cloned cDNA sequence data (3-5). Enzyme activity for the "platelet-type" 12-lipoxygenase (P-12LO) was first found in human platelets more than 20 years ago (6). P-12LO has been found to be the predominant isoform in epidermal skin specimens and A431 epidermoid cells (5, 7-9). The other 12-lipoxygenase, referred to as "leukocyte-type," was first characterized extensively from porcine leukocytes (10) and was found to have a rather broad distribution in porcine and canine tissues by immunochemical assays (11,12). Besides tissue distribution, the leukocyte-type 12-lipoxygenase (L-12LO) is distinguished from the platelet-type enzyme by its ability to form 15-HPETE in addition to 12-HPETE from arachidonic acid substrate. L-12LO is highly related to 15LO in that both are dual specificity lipoxygenases, and they are about 85% identica...

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5-Lipoxygenase is not essential in macrophage-mediated oxidation of low-density lipoprotein

Cited by 66 publications

References 22 publications

Leukotriene Signaling in Atherosclerosis and Ischemia

Leukotriene Signaling in Atherosclerosis and Ischemia

Peroxynitrite modification of low‐density lipoprotein leads to recognition by the macrophage scavenger receptor

Disruption of 12/15-Lipoxygenase Expression in Peritoneal Macrophages

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