Oxidation, Lipoxygenase, and Atherogenesis

Sigal, Elliott; Laughton, Craig W.; Mulkins, Mary A.

doi:10.1111/j.1749-6632.1994.tb12046.x

Cited by 42 publications

(23 citation statements)

References 66 publications

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“…cDNA was synthesized using oligo(dT) [12][13][14][15][16][17][18] as a primer and SuperScript II reverse transcriptase. PCR was carried out with ExTaq DNA polymerase and primers as shown in Table I under the following conditions: denaturation at 94°C for 1 min, annealing at 55°C for 30 s, and extension at 72°C for 1 min.…”

Section: Methodsmentioning

confidence: 99%

“…Macrophages are likely candidates to mediate in vivo LDL oxidation, because they are accumulated in the atherosclerosis lesions and are capable of in vitro LDL oxidation in culture medium free of metal ion additives (11). A number of evidences suggest that the 12/15-lipoxygenase present in monocyte-macrophage contributes to the cell-mediated LDL oxidation (12,13). Incubation of LDL with 12/15-lipoxygenase led to significant oxidation of LDL (14,15).…”

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confidence: 99%

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Low Density Lipoprotein Receptor-related Protein Is Required for Macrophage-mediated Oxidation of Low Density Lipoprotein by 12/15-Lipoxygenase

Xu¹,

Takahashi²,

Sakashita³

et al. 2001

Journal of Biological Chemistry

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The oxidative modification of low density lipoprotein (LDL) has been implicated in the early stage of atherosclerosis through multiple potential pathways, and 12/ 15-lipoxygenase is suggested to be involved in this oxidation process. We demonstrated previously that the 12/15-lipoxygenase overexpressed in mouse macrophage-like J774A.1 cells was required for the cell-mediated LDL oxidation. However, the mechanism of the oxidation of extracellular LDL by the intracellular 12/ 15-lipoxygenase has not yet been elucidated. In the present study, we found that not only the LDL receptor but also LDL receptor-related protein ( Lipoxygenases are a class of enzymes that incorporate one molecular oxygen into unsaturated fatty acids giving rise to their hydroperoxy derivatives. There are 5-, 8-, 12-, and 15-lipoxygenases in mammalian tissues, named according to the number of carbon atoms of arachidonic acid to be oxygenated (1-4). The 12-lipoxygenase subfamily includes leukocyte, platelet, and epidermal isoforms. 15-Lipoxygenase-1 was first isolated from reticulocytes, and 15-lipoxygenase-2 was cloned from hair follicles (3). Because the leukocyte 12-lipoxygenase and 15-lipoxygenase-1 are highly related in their primary structures and enzymological properties and are abundant in various tissues of many species, these enzymes are called collectively 12/15-lipoxygenases (2, 5). Although the pathophysiological functions of the 12/15-lipoxygenases are still a subject of investigation and discussion, recent research progress has revealed the involvement of the enzymes in the development of atherosclerosis (6 -8).The oxidative modification of low density lipoprotein (LDL) We previously demonstrated that 12/15-lipoxygenase overexpressed in mouse macrophage-like J774A.1 cells was involved essentially in the oxidation of LDL based upon the stereospecific oxygenation of esterified unsaturated fatty acid in LDL (21). This fact suggests direct interaction of the enzyme with LDL or the transfer of cellular lipids oxygenated by the enzyme to LDL. Secretion or leakage of the 12/15-lipoxygenase to the medium was ruled out (21). As the mechanism of the cell-mediated oxidation of extracellular LDL, we postulate that binding of native LDL to cell surface receptors is the first step in the 12/15-lipoxygenase-expressing cells. Among such receptors, the LDL receptor plays an important role in LDL metabolism in liver and steroidogenic tissues. However, the LDL receptor is not expressed in the intima of normal or atherosclerotic arteries (22). Importantly, the LDL receptor is not required in the cell-mediated LDL oxidation as shown by in vitro experiments (23) and LDL receptor-deficient mice studies (20,24). The native LDL also binds to LDL receptor-related protein

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Low Density Lipoprotein Receptor-related Protein Is Required for Macrophage-mediated Oxidation of Low Density Lipoprotein by 12/15-Lipoxygenase

Xu¹,

Takahashi²,

Sakashita³

et al. 2001

Journal of Biological Chemistry

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“…28 13-HPODE is the oxidized product of linoleic acid produced by lipoxygenases. 29,30 13-HPODE induces apoptosis in smooth muscle cells and also increases proto-oncogene expression. [5][6][7] Therefore, we incubated 13-HPODE with both transfected and untransfected cells and measured [ 3 H]thymidine incorporation and cytotoxicity by MTT assay.…”

Section: Effect Of 13-hpode On Catalase-transfected Cellsmentioning

confidence: 99%

Overexpression of Human Catalase Gene Decreases Oxidized Lipid-Induced Cytotoxicity in Vascular Smooth Muscle Cells

Santanam

Augé

Zhou

et al. 1999

ATVB

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Abstract-Reactive oxygen metabolites such as hydrogen peroxide (H 2 O 2 ) and oxidized fatty acids are proinflammatory and are involved in the pathophysiology of various diseases including atherosclerosis. The effects of these oxidants could be inhibited by the external addition of an antioxidant, suggesting the promotion or propagation of further oxidation. In this study, we describe the stable overexpression of human catalase in smooth muscle cells and the resistance of these cells to cytotoxicity induced not only by the addition of H 2 O 2 but also by the addition of 13-hydroperoxyoctadecadienoic acid (13-HPODE). The results pose an intriguing possibility of the generation of H 2 O 2 from a peroxidized fatty acid. Accordingly, incubation of cells with both 13-HPODE and 13-hydroxyoctadecadienoic acid resulted in the generation of intracellular H 2 O 2 . To explain the observed results by which catalase could overcome the effects of 13-HPODE, we propose that oxidized fatty acids are degraded in the cellular peroxisomes, resulting in the generation of H 2 O 2 . In other words, the cellular effects of peroxidized fatty acids could be attributed to the generation of H 2 O 2 .

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“…Oxylipin biosynthesis is initiated by the enzyme lipoxygenase (LOX; EC1.13.11.12), which is ubiquitous in plants and mammals and catalyses the hydroperoxidation of polyunsaturated fatty acids for further conversion into volatile aldehydes and JAs in plants (Mosblech et al, 2009), into diols and lactones in fungi (Tsitsigiannis and Keller, 2007), and into lipoxins and leukotrienes in mammals (Samuelsson et al, 1987;Sigal et al, 1994). In plants, two types of LOX, 13-LOX and 9-LOX, catalyse the formation of two different isomer products, (13S)-and (9S)-hydroperoxyoctadecadienoic acids (13-and 9-HPOD) by introducing molecular oxygen at either carbon atom 13 or carbon atom 9, respectively, of the hydrocarbon backbone (Wasternack, 2007).…”

Section: Introductionmentioning

confidence: 99%

PgLOX6 encoding a lipoxygenase contributes to jasmonic acid biosynthesis and ginsenoside production in Panax ginseng

Rahimi

Kim

Sukweenadhi

et al. 2016

EXBOTJ

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Ginsenosides, the valuable pharmaceutical compounds in Panax ginseng, are triterpene saponins that occur mainly in ginseng plants. It was shown that in vitro treatment with the phytohormone jasmonic acid (JA) is able to increase ginsenoside production in ginseng plants. To understand the molecular link between JA biosynthesis and ginsenoside biosynthesis, we identified a JA biosynthetic 13-lipoxygenase gene (PgLOX6) in P. ginseng that promotes ginsenoside production. The expression of PgLOX6 was high in vascular bundles, which corresponds with expression of ginsenoside biosynthetic genes. Consistent with the role of PgLOX6 in synthesizing JA and promoting ginsenoside synthesis, transgenic plants overexpressing PgLOX6 in Arabidopsis had increased amounts of JA and methyl jasmonate (MJ), increased expression of triterpene biosynthetic genes such as squalene synthase (AtSS1) and squalene epoxidase (AtSE1), and increased squalene content. Moreover, transgenic ginseng roots overexpressing PgLOX6 had around 1.4-fold increased ginsenoside content and upregulation of ginsenoside biosynthesis-related genes including PgSS1, PgSE1, and dammarenediol synthase (PgDDS), which is similar to that of treatment with MJ. However, MJ treatment of transgenic ginseng significantly enhanced JA and MJ, associated with a 2.8-fold increase of ginsenoside content compared with the non-treated, non-transgenic control plant, which was 1.4 times higher than the MJ treatment effect on non-transgenic plants. These results demonstrate that PgLOX6 is responsible for the biosynthesis of JA and promotion of the production of triterpenoid saponin through up-regulating the expression of ginsenoside biosynthetic genes. This work provides insight into the role of JA in biosynthesizing secondary metabolites and provides a molecular tool for increasing ginsenoside production.

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Oxidation, Lipoxygenase, and Atherogenesis

Cited by 42 publications

References 66 publications

Low Density Lipoprotein Receptor-related Protein Is Required for Macrophage-mediated Oxidation of Low Density Lipoprotein by 12/15-Lipoxygenase

Low Density Lipoprotein Receptor-related Protein Is Required for Macrophage-mediated Oxidation of Low Density Lipoprotein by 12/15-Lipoxygenase

Overexpression of Human Catalase Gene Decreases Oxidized Lipid-Induced Cytotoxicity in Vascular Smooth Muscle Cells

PgLOX6 encoding a lipoxygenase contributes to jasmonic acid biosynthesis and ginsenoside production in Panax ginseng

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