Transformation of epithelial cells stably transfected with HO-generating peroxisomal urate oxidase

Chu, Ruiyin; Yang, Lin; Reddy, Kritika; Pan, C-H.; Rao, M. Sambasiva; Reddy, J. K.; Yeldandi, Anjana V.

doi:10.1016/s0928-4346(97)89834-9

Cited by 25 publications

(29 citation statements)

References 14 publications

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“…In addition, that FAO is a link between peroxisome proliferators and NF-k B activation raises the possibility that NF-k B is involved in the tum or-promoting activities of these agents. This idea would be consistent with the recent data of Chu and associates, who found that overexpressing the H 2 O 2 -generating enzym es FAO or urate oxidase in CV1 cells led to anchorage-independent cell growth and allowed these cells to develop into tumors in nude mice (Chu et al, 1995(Chu et al, , 1996.…”

Section: Discussionsupporting

confidence: 91%

Expression of the Hydrogen Peroxide-Generating Enzyme Fatty Acyl CoA Oxidase Activates NF-kappa B

Li¹,

Tharappel²,

Cooper³

et al. 2000

DNA and Cell Biology

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Peroxisome proliferators are a class of hepatic carcinogens in rodents and have been proposed to act in part by increasing oxidative stress. Fatty acyl CoA oxidase (FAO), which is highly induced by peroxisome proliferators, is the hydrogen peroxide-generating enzyme of the peroxisomal beta-oxidation pathway. We previously showed that the treatment of rats and mice with the peroxisome proliferator ciprofibrate resulted in increased hepatic NF-kappaB activity and suggested that this effect may be secondary to the action of H2O-generating enzymes. To test this possibility directly, we have determined whether transient overexpression of FAO, in the absence of peroxisome proliferators, leads to NF-kappaB activation. Here, we show that FAO overexpression in Cos-1 cells, in the presence of an H2O-generating substrate, can activate a NF-kappaB regulated reporter gene. Electrophoretic mobility shift assays further demonstrated that FAO expression increases nuclear NF-kappaB DNA binding activity in a dose-dependent manner. The antioxidants vitamin E and catalase can inhibit this activation. These results indicate that FAO mediates, at least in part, peroxisome proliferator-induced NF-kappaB activation.

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Section: Discussionsupporting

confidence: 91%

Expression of the Hydrogen Peroxide-Generating Enzyme Fatty Acyl CoA Oxidase Activates NF-kappa B

Li¹,

Tharappel²,

Cooper³

et al. 2000

DNA and Cell Biology

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“…Lack of protective systems in knockout mice such as lack of peroxiredoxin or glutathione (GSH) peroxidases indeed leads to malignant cancers [51,52]. Transfection of an H2O2-generating system transforms epithelial cells [53]. High-level acute H2O2 treatment of various cells in vitro leads to apoptosis [54].…”

Section: Toxic Effects Of H2o2mentioning

confidence: 99%

Oxidative Stress and Antioxidant Status in Hypo- and Hyperthyroidism

Petrulea¹,

Muresan²,

Duncea³

2012

Antioxidant Enzyme

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“…In such transfected cells H 2 O 2 production increased significantly after exposure to corresponding substrates when compared to corresponding untransfected controls. After 60 days of exposure to uric acid or the fatty acid substrate, the cells developed features of malignant transformation and formed tumors after injection to nude mice (Chu et al 1995(Chu et al , 1996Yeldandi et al 2000). Thus, it seems that indeed peroxisomal oxidases when overexpressed in cells can lead to neoplastic transformation.…”

Section: Peroxisome Proliferation and Induction Of Rosmentioning

confidence: 99%

Mammalian peroxisomes and reactive oxygen species

Schrader

Fahimi

2004

Histochem Cell Biol

154

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The central role of peroxisomes in the generation and scavenging of hydrogen peroxide has been well known ever since their discovery almost four decades ago. Recent studies have revealed their involvement in metabolism of oxygen free radicals and nitric oxide that have important functions in intra- and intercellular signaling. The analysis of the role of mammalian peroxisomes in a variety of physiological and pathological processes involving reactive oxygen species (ROS) is the subject of this review. The general characteristics of peroxisomes and their enzymes involved in the metabolism of ROS are briefly reviewed. An expansion of the peroxisomal compartment with proliferation of tubular peroxisomes is observed in cells exposed to UV irradiation and various oxidants and is apparently accompanied by upregulation of PEX genes. Significant reduction of peroxisomes and their enzymes is observed in inflammatory processes including infections, ischemia-reperfusion injury, and allograft rejection and seems to be related to the suppressive effect of tumor necrosis factor-alpha on peroxisome function and peroxisome proliferator activated receptor-alpha. Xenobiotic-induced proliferation of peroxisomes in rodents is accompanied by the formation of hepatic tumors, and evidently the imbalance in generation and decomposition of ROS plays an important role in this process. In PEX5-/- knockout mice lacking functional peroxisomes severe alterations of mitochondria in various organs are observed which seem to be due to a generalized increase in oxidative stress confirming the important role of peroxisomes in homeostasis of ROS and the implications of its disturbances for cell pathology.

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Transformation of epithelial cells stably transfected with HO-generating peroxisomal urate oxidase

Cited by 25 publications

References 14 publications

Expression of the Hydrogen Peroxide-Generating Enzyme Fatty Acyl CoA Oxidase Activates NF-kappa B

Expression of the Hydrogen Peroxide-Generating Enzyme Fatty Acyl CoA Oxidase Activates NF-kappa B

Oxidative Stress and Antioxidant Status in Hypo- and Hyperthyroidism

Mammalian peroxisomes and reactive oxygen species

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