Antioxidant effect of diethyldithiocarbamate on microsomal lipid peroxidation assessed by low‐level chemiluminescence and alkane production

Bartoli, Gianna Maria; Müller, A.; Cadenas, Enrique; Sies, Helmut

doi:10.1016/0014-5793(83)80319-6

Cited by 60 publications

(19 citation statements)

References 15 publications

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“…Indeed, iron has a key role in both the initiation and propagation of lipid peroxidation, leading to the generation of peroxyl and alkoxyl radicals as well as lipid peroxides (58). A role for iron-catalyzed lipid peroxidation was further suggested by the fact that DDTC, DFO, and TEMPO all have well documented inhibitory effects on iron-catalyzed membrane lipid peroxidation (33,36,37). In addition, there are a number of reports in the literature implicating lipid peroxidation in pathways to NF-B.…”

Section: Discussionmentioning

confidence: 99%

“…TNF, but Not IL-1 or H 2 O 2 , Increases Lipid Peroxidation in ECV304 Cells-DFO, DDTC, and TEMPO have well documented inhibitory effects on lipid peroxidation (33,36,37). Since lipid peroxidation has been implicated in NF-B activation in some systems (14, 38 -40), we therefore determined whether this was important for the difference between IL-1 and TNF here.…”

Section: Hydrogen Peroxide Activates Nf-b In Ecv304 Cells But Not Huvmentioning

confidence: 96%

“…The predominant form of NF-B activated in cells is a p50/RelA heterodimer, which is associated with IB␣ in resting cells. Upon stimulation with agents such as IL-1 and TNF, IB␣ is rapidly phosphorylated on two serine residues (Ser 32 and Ser 36 ), which targets the inhibitor protein for ubiquitination and subsequent degradation by the 26 S proteasome (reviewed in Ref. 7).…”

mentioning

confidence: 99%

“…Thus, it is likely that agents that activate NF-B do so through the activation of a specific IB␣ kinase or, alternatively, by inactivating a particular phosphatase. A high molecular mass kinase complex that phosphorylates IB␣ on Ser 32 and Ser 36 has been identified (8).…”

mentioning

confidence: 99%

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Lipid Peroxidation Is Involved in the Activation of NF-κB by Tumor Necrosis Factor but Not Interleukin-1 in the Human Endothelial Cell Line ECV304

Bowie¹,

Moynagh²,

O’Neill³

1997

Journal of Biological Chemistry

178

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It has been proposed that reactive oxygen species, and in particular H 2 O 2 , may be involved in the activation of NF-B by diverse stimuli in different cell types. Here we have investigated the effect of a range of putative antioxidants on NF-B activation by interleukin-1 and tumor necrosis factor as well as the ability of H 2 O 2 to activate NF-B in primary human umbilical vein endothelial cells and the transformed human endothelial cell line ECV304. Activation of NF-B and stimulation of IB␣ degradation by H 2 O 2 was only evident in the transformed cells and required much longer contact times than that observed with interleukin-1 or tumor necrosis factor. Furthermore, only H 2 O 2 was sensitive to Nacetyl-L-cysteine, and no increase in H 2 O 2 was detected in response to either cytokine. Pyrrolidine dithiocarbamate has been purported to be a specific antioxidant inhibitor of NF-B that acts independently of activating agent or cell type. However, we found that tumor necrosis factor-but not interleukin-1-driven NF-B activation and IB␣ degradation were sensitive to pyrrolidine dithiocarbamate in transformed cells, while neither pathway was inhibited in primary cells. Phorbol ester-mediated activation was sensitive in both transformed and primary cells. Other antioxidants failed to inhibit either cytokine, while the iron chelators desferrioxamine and 2,2,6,6-tetramethylpiperidine-1-oxyl mimicked the pattern of inhibition seen for the dithiocarbamate. This suggested that pyrrolidine dithiocarbamate was inhibiting NF-B activation in endothelial cells primarily through its iron-chelating properties. Tumor necrosis factor, but not interleukin-1, was found to induce lipid peroxidation in ECV304 cells. This was inhibited by pyrrolidine dithiocarbamate and desferrioxamine. t-Butyl hydroperoxide, which induces lipid peroxidation, activated NF-B. Finally, butylated hydroxyanisole, which inhibits lipid peroxidation but has no iron-chelating properties, inhibited NF-B activation by tumor necrosis factor but not interleukin-1.Taken together, the results argue against a role for H 2 O 2 in NF-B activation by cytokines in endothelial cells. Furthermore, tumor necrosis factor and interleukin-1 activate NF-B through different mechanisms in ECV304 cells, with the tumor necrosis factor pathway involving iron-catalyzed lipid peroxidation.The inducible, higher eukaryotic transcription factor NF-B has an important role in the regulation of a number of genes involved in immune and inflammatory responses. It is activated in many cell types by a wide range of stimuli including the proinflammatory cytokines interleukin-1 (IL-1) 1 and tumor necrosis factor (TNF) and the protein kinase C activator phorbol 12-myristate 13-acetate (PMA) (reviewed in Ref. 1).In endothelial cells (ECs), activation of NF-B is central to the regulation of many genes by IL-1 and TNF such as the cell adhesion molecules vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and E-selectin (2) and tissue factor (3). Recently, NF-B has been identified ...

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Section: Discussionmentioning

confidence: 99%

Section: Hydrogen Peroxide Activates Nf-b In Ecv304 Cells But Not Huvmentioning

confidence: 96%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Lipid Peroxidation Is Involved in the Activation of NF-κB by Tumor Necrosis Factor but Not Interleukin-1 in the Human Endothelial Cell Line ECV304

Bowie¹,

Moynagh²,

O’Neill³

1997

Journal of Biological Chemistry

178

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“…It has been reported that DDC inhibits microsomal lipid peroxidation in rat hepatocytes [25] and DNA breakage induced by hydroxyl radical (W OH) [26]. DDC has been used for the treatment of oxygen toxicity in the central nervous system [27,28] and in alleviating the side effects of cancer [29] and HIV treatment [30].…”

Section: Introductionmentioning

confidence: 99%

Preventive Effect of Diethyldithiocarbamate on Selenite-Induced Opacity in Cultured Rat Lenses

Ito

Cai²,

Terao

et al. 2000

Ophthalmic Res

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Increasing evidence suggests the involvement of reactive oxygen species in the development of cataracts. In this study, we investigated the preventive effect of diethyldithiocarbamate (DDC) on the selenite-induced opacification of cultured rat lenses. Lens opacity was produced by incubation with 0.2 mM selenite for 24 h, which resulted in an increase in selenium content in the cultured lenses. The increase in selenium content and the onset of opacification and lens membrane damage were inhibited by preincubation with DDC. It is reasonable to assume that DDC contributed to anticataract ability. In addition, selenite resulted in a significant decrease in glutathione and protein thiol content and an increase in lipid peroxidation levels in the lenses. These alterations were also depressed by DDC, suggesting a contribution of an antioxidative effect by DDC in the inhibition of lens opacification. At the same lens selenium content, DDC treatment inhibited opacification and lipid peroxide. In conclusion, we propose that the antioxidative properties of DDC play a major role in its contribution to the anticataract effect.

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Effects of antioxidants and haemoglobin status on the t‐butyl hydroperoxide‐induced oxygen uptake by red blood cells

Lissi

Franz

Cabezas

et al. 1986

Cell Biochemistry & Function

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Oxygen uptake by erythrocytes exposed to t-butyl hydroperoxide (t-BHP) exhibited an induction period. The rate of oxygen consumption can be reduced by antioxidants and blood plasma. The induction time was not appreciably modified by the antioxidants tested, however, plasma increased it by a factor of two. The in vivo pretreatment with diethyl maleate (0.6 g kg-1) produced increased rates of oxygen uptake without changes in the induction period, while vitamin E (12.5 mg kg-1) elicited lower oxygen consumption rates and longer induction times, compared to those observed in cells from control rats upon addition of the hydroperoxide. These results suggest that the antioxidants tested on the t-BHP lipid peroxidation in erythrocyte suspensions act as inhibitors and/or retarders of the process. Furthermore, lipid peroxidation induced in these conditions seems to depend upon the haemoglobin status of the cells as oxygen uptake, malondialdehyde production and chemiluminescence were significantly higher in methaemoglobin-containing cells than in those containing oxyhaemoglobin.

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Antioxidant effect of diethyldithiocarbamate on microsomal lipid peroxidation assessed by low‐level chemiluminescence and alkane production

Cited by 60 publications

References 15 publications

Lipid Peroxidation Is Involved in the Activation of NF-κB by Tumor Necrosis Factor but Not Interleukin-1 in the Human Endothelial Cell Line ECV304

Lipid Peroxidation Is Involved in the Activation of NF-κB by Tumor Necrosis Factor but Not Interleukin-1 in the Human Endothelial Cell Line ECV304

Preventive Effect of Diethyldithiocarbamate on Selenite-Induced Opacity in Cultured Rat Lenses

Effects of antioxidants and haemoglobin status on the t‐butyl hydroperoxide‐induced oxygen uptake by red blood cells

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