Arsenic Inhibits NF-κB-mediated Gene Transcription by Blocking IκB Kinase Activity and IκBα Phosphorylation and Degradation

Roussel, Robert R.; Barchowsky, Aaron

doi:10.1006/abbi.2000.1770

Cited by 114 publications

(67 citation statements)

References 42 publications

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“…However, oxidative stress activates activator protein-1 (AP-1) in human keratinocytes and other cells (65,66) and may contribute to elevated nad(p)h quinone oxidoreductase (known to be regulated by AP-1 and nuclear factor kappa B [NF-κB]) expression after arsenite exposure. This notion is further supported by arsenic-induced modulation of c-jun and c-fos in vitro and in vivo (67)(68)(69) and NF-κB activity in vitro (70,71). We proposed that reducing cellular GSH levels with a specific inhibitor of GSH synthesis (BSO) could exacerbate the gene expression-modifying effects of arsenite on NHEK.…”

Section: Smentioning

confidence: 69%

Sodium arsenite-induced stress-related gene expression in normal human epidermal, HaCaT, and HEL30 keratinocytes.

Trouba

Geisenhoffer

Germolec

2002

Environ Health Perspect

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Arsenic is a carcinogen that poses a significant health risk in humans. Based on evidence that arsenic has differential effects on human, rodent, normal, and transformed cells, these studies addressed the relative merits of using normal human epidermal keratinocytes (NHEK) and immortalized human (HaCaT) and mouse (HEL30) keratinocytes when examining stressinduced gene expression that may contribute to carcinogenesis. We hypothesize that redox-related gene expression is differentially modulated by arsenic in normal versus immortalized keratinocytes. To test the hypothesis, we exposed keratinocytes to sodium arsenite for 4 or 24 hr, at which time serine threonine kinase-25 (

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Section: Smentioning

confidence: 69%

Sodium arsenite-induced stress-related gene expression in normal human epidermal, HaCaT, and HEL30 keratinocytes.

Trouba

Geisenhoffer

Germolec

2002

Environ Health Perspect

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“…Thus, the loss of Raf-1 reduced NO production in LPS-stimulated RAW cells through the inhibition of NF-B and Erk activity, demonstrating that Raf-1 plays a critical role in LPSinduced NO production in macrophages. In addition, SA is reported to inhibit NF-B-mediated gene transcription by blocking I B kinase activity and I B-␣ phosphorylation and degradation (28).…”

Section: Discussionmentioning

confidence: 99%

The Inhibitory Action of Sodium Arsenite on Lipopolysaccharide-Induced Nitric Oxide Production in RAW 267.4 Macrophage Cells: A Role of Raf-1 in Lipopolysaccharide Signaling

Chakravortty

Kato

Sugiyama

et al. 2001

The Journal of Immunology

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The effect of sodium arsenite (SA) on LPS-induced NO production in RAW 267.4 murine macrophage cells was studied. SA pretreatment of LPS-stimulated RAW cells resulted in a striking reduction in NO production. No significant difference in LPS binding was observed between RAW cells pretreated with SA and control untreated RAW cells, suggesting that SA might impair the intracellular signal pathway for NO production. SA inhibited LPS-induced NF-κB activation by preventing loss of IκB-α and -β. Furthermore, SA blocked phosphorylation of extracellular signal-regulated kinase 1/2 (Erk1/2), but not phosphorylation of p38 and c-Jun N-terminal kinase. SA treatment resulted in the disappearance of Raf-1, suggesting that it might cause the inhibition of the Erk1/2 mitogen-activated protein (MAP) kinase pathway. The SA-mediated loss of Raf-1 also abolished LPS-induced NF-κB activation as well as the Erk1/2 pathway. The dominant negative mutant of MAP kinase kinase 1 inhibited both NO production and NF-κB activation in LPS-stimulated RAW cells. Taken together, these results indicate that the inhibitory action of SA on NO production in LPS-stimulated macrophages might be due to abrogation of inducible NO synthase induction, and it might be closely related to inactivation of the NF-κB and Erk1/2 MAP kinase pathways through loss of Raf-1.

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“…Arsenic compounds are believed to block the NF-kB pathway by inhibiting the IKK complex (Kapahi et al, 2000;Roussel and Barchowsky, 2000). We have previously shown that arsenic trioxide, phenylarsine oxide (PAO) and arsenic acid and are potent inhibitors of K13-induced NF-kB activation (Matta et al, 2003).…”

Section: Nature and Subunit Composition Of K13-induced Transcription mentioning

confidence: 99%

Induction of IL-8 expression by human herpesvirus 8 encoded vFLIP K13 via NF-κB activation

Sun

Matta

et al. 2006

Oncogene

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Arsenic Inhibits NF-κB-mediated Gene Transcription by Blocking IκB Kinase Activity and IκBα Phosphorylation and Degradation

Cited by 114 publications

References 42 publications

Sodium arsenite-induced stress-related gene expression in normal human epidermal, HaCaT, and HEL30 keratinocytes.

Sodium arsenite-induced stress-related gene expression in normal human epidermal, HaCaT, and HEL30 keratinocytes.

The Inhibitory Action of Sodium Arsenite on Lipopolysaccharide-Induced Nitric Oxide Production in RAW 267.4 Macrophage Cells: A Role of Raf-1 in Lipopolysaccharide Signaling

Induction of IL-8 expression by human herpesvirus 8 encoded vFLIP K13 via NF-κB activation

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