Inhibition of Arachidonate Metabolism in Human Epidermoid Carcinoma A431 Cells Overexpressing Phospholipid Hydroperoxide Glutathione Peroxidase

Chen, Ching-Jiunn; Huang, Hung-Fu; Chang, Wen-Chang

doi:10.1159/000064556

Cited by 2 publications

(3 citation statements)

References 18 publications

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“…90,91 Experiments with human epidermoid carcinoma A431 cells that were transfected with the cDNA sequence of cytoplasmic PH-GPx revealed that PH-GPx downregulates the 12-LOX activity. 92 In animals, platelets 12-LOX, 15-LOX and COX-2 are more sensitive to PH-GPx inhibition than do 5-LOX and COX-1, which are more resistant. 93 This inhibition is probably caused by a requirement of fatty acid hydroperoxides for the activation of LOX and COX that are regulated by its own products.…”

Section: Sources Of Free Radicals During Inflammationmentioning

confidence: 99%

Chronic inflammation and oxidative stress in human carcinogenesis

Federico

Morgillo

Tuccillo

et al. 2007

Intl Journal of Cancer

844

583

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A wide array of chronic inflammatory conditions predispose susceptible cells to neoplastic transformation. In general, the longer the inflammation persists, the higher the risk of cancer. A mutated cell is a sine qua non for carcinogenesis. Inflammatory processes may induce DNA mutations in cells via oxidative/nitrosative stress. This condition occurs when the generation of free radicals and active intermediates in a system exceeds the system's ability to neutralize and eliminate them. Inflammatory cells and cancer cells themselves produce free radicals and soluble mediators such as metabolites of arachidonic acid, cytokines and chemokines, which act by further producing reactive species. These, in turn, strongly recruit inflammatory cells in a vicious circle. Reactive intermediates of oxygen and nitrogen may directly oxidize DNA, or may interfere with mechanisms of DNA repair. These reactive substances may also rapidly react with proteins, carbohydrates and lipids, and the derivative products may induce a high perturbation in the intracellular and intercellular homeostasis, until DNA mutation. The main substances that link inflammation to cancer via oxidative/nitrosative stress are prostaglandins and cytokines. The effectors are represented by an imbalance between pro-oxidant and antioxidant enzyme activities (lipoxygenase, cyclooxygenase and phospholipid hydroperoxide glutathione-peroxidase), hydroperoxides and lipoperoxides, aldehydes and peroxinitrite. This review focalizes some of these intricate events by discussing the relationships occurring among oxidative/nitrosative/metabolic stress, inflammation and cancer. ' 2007 Wiley-Liss, Inc.

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Section: Sources Of Free Radicals During Inflammationmentioning

confidence: 99%

Chronic inflammation and oxidative stress in human carcinogenesis

Federico

Morgillo

Tuccillo

et al. 2007

Intl Journal of Cancer

844

583

View full text Add to dashboard Cite

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“…Using an intact cell assay system, the metabolism of arachidonic acid to PGE 2 catalyzed by cyclooxygenase 1 was significantly decreased in stable transfectants overexpressing PHGPx when compared to that in a vector control cell line [6]. If the intact cell assay is carried out in the presence of 13-HPODE as a stimulator of lipid peroxidation, formation of 12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE] from arachidonic acid is also significantly decreased in stable transfectants of overexpressing PHGPx when compared to that in a vector control cell line, indicating that PHGPx downregulates the 12(S)-lipoxygenase activity in A431 cells [6]. In accordance with our results in the study of 12(S)-lipoxygenase and cyclooxygenase 1, overexpression of PHGPx in RBL-2H3 cells also significantly suppresses the production of 5-lipoxygenase-catalyzed leukotrienes [25] and cyclooxygenase 2-catalyzed PGD 2 [45].…”

Section: Overexpression Of Phgpx Inhibits Arachidonate Oxygenation Inmentioning

confidence: 99%

“…The basal production of PGE 2 by A431 cells is from the metabolism of arachidonic acid by cyclooxygenase 1 since PGE 2 formation is inhibited by the treatment of the cells with indomethacin but not by the specific cyclooxygenase 2 inhibitor NS398 [7]. Using an intact cell assay system, the metabolism of arachidonic acid to PGE 2 catalyzed by cyclooxygenase 1 was significantly decreased in stable transfectants overexpressing PHGPx when compared to that in a vector control cell line [6]. If the intact cell assay is carried out in the presence of 13-HPODE as a stimulator of lipid peroxidation, formation of 12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE] from arachidonic acid is also significantly decreased in stable transfectants of overexpressing PHGPx when compared to that in a vector control cell line, indicating that PHGPx downregulates the 12(S)-lipoxygenase activity in A431 cells [6].…”

Section: Overexpression Of Phgpx Inhibits Arachidonate Oxygenation Inmentioning

confidence: 99%

Identification of an Endogenous Inhibitor of Arachidonate Metabolism in Human Epidermoid Carcinoma A431 Cells

Chang

2003

J Biomed Sci

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Eicosanoids, which include prostaglandins, thromboxanes, and leukotrienes, are produced from arachidonic acid by three main pathways in cells, including cyclooxygenases and lipoxygenases, and cytochrome P450 enzymes. Accumulated evidence indicates that a certain peroxide tone is required for the initiation of reaction by lipoxygenases and cyclooxygenases. An endogenous inhibitor of arachidonate oxygenation was suspected in the cytosolic fraction of human epidermoid carcinoma A431 cells. After a series of studies, the existence of this inhibitor was confirmed, while it was purified and characterized. By amino acid sequence analysis, the inhibitor in A431 cells was subsequently identified as a phospholipid hydroperoxide glutathione peroxidase (PHGPx). Depletion of cellular glutathione in cells by diethyl maleate or by dibuthionine-sulfoximine results in an increase in enzyme activities of 12(S)-lipoxygenase and cyclooxygenase, suggesting that glutathione-depleting agents abolish the enzyme activity of PHGPx in cells. Stable transfectants of A431 cells with overexpression and depletion of PHGPx have been constructed, respectively. Reduction of arachidonate metabolism through 12(S)-lipoxygenase and cyclooxygenase 1 and that of the arsenite-induced generation of reactive oxygen species are observed in cells overexpressing PHGPx. On the other hand, enhancement of arachidonate metabolism and the arsenite-induced generation of reactive oxygen species is detected in PHGPx-depleted cells. In conclusion, the endogenous inhibitor of arachidonate metabolism present in A431 cells is a PHGPx, which plays a functional role in the down-regulation of arachidonate oxygenation catalyzed by 12(S)-lipoxygenase and cyclooxygenase 1 through the reduction of the level of intracellular lipid hydroperoxides. The latter acts as the peroxide tone for arachidonate metabolism in A431 cells.

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Inhibition of Arachidonate Metabolism in Human Epidermoid Carcinoma A431 Cells Overexpressing Phospholipid Hydroperoxide Glutathione Peroxidase

Cited by 2 publications

References 18 publications

Chronic inflammation and oxidative stress in human carcinogenesis

Chronic inflammation and oxidative stress in human carcinogenesis

Identification of an Endogenous Inhibitor of Arachidonate Metabolism in Human Epidermoid Carcinoma A431 Cells

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