Arsenic-induced NFkappaB transactivation through Erks- and JNKs-dependent pathways in mouse epidermal JB6 cells.

Molecular and cellular biochemistry ·Vol. 222 ·No. 1-2 ·2001-06-00 ·Pages 29-34

Huang C, Li J, Ding M, Wang L, Shi X, Castranova V, Vallyathan V, Ju G, Costa M

Abstract

Tumor promoting effects of arsenic are believed to be associated with its transactivation activity on transcription factors, such as AP-1 and NFkappaB. However, the results from different groups studying the effects of arsenic on NFkappaB activation are contradictory in different cell models. Since arsenic is a strong skin carcinogen, we have investigated the activation of NFkappaB by arsenic in a mouse skin epidermal cell line, JB6 cells. Exposure of cells to arsenite or arsenate led to NFkappaB transactivation in mouse epidermal JB6 NFkappaB-luciferase reporter stable transfectants, C141 NFkappaB mass1. This induction of NFkappaB activity by arsenic was dose- and time-dependent. The transactivation of NFkappaB by arsenic appeared to be through activation of Erks and JNKs pathways because increased NFkappaB activity by arsenic could be dramatically inhibited by either pre-treatment of cells with PD98059 or overexpression of dominant negative JNK1. That Erks activation is required for arsenic-induced NFkappaB transactivation was further supported by the findings that arsenic-induced NFkappaB transactivation was impaired in JB6 30.7b cells, which were deficient in Erks.

MeSH Terms

Animals Arsenates/pharmacology Arsenic/pharmacology Arsenites/pharmacology Cell Line Drug Interactions Enzyme Inhibitors/pharmacology Epidermal Cells Epidermis/drug effects,enzymology Flavonoids/pharmacology JNK Mitogen-Activated Protein Kinases MAP Kinase Signaling System/drug effects Mice Mitogen-Activated Protein Kinases/metabolism NF-kappa B/biosynthesis Transcriptional Activation/drug effects

Chemicals

Arsenates Arsenites Enzyme Inhibitors Flavonoids NF-kappa B JNK Mitogen-Activated Protein Kinases Mitogen-Activated Protein Kinases Arsenic 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one

Authors & Affiliations

9 authors, click to expand affiliations / ORCID

Huang C

Nelson Institute of Environmental Medicine, New York University School of Medicine, NY 10016, USA.

Li J

Ding M

Wang L

Shi X

Castranova V

Vallyathan V

Ju G

Costa M

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Article Info

Journal

Molecular and cellular biochemistry

Abbr.

Mol Cell Biochem

ISSN

0300-8177

Published

2001-06-00

Pages

29-34

Language

English

Region

Netherlands

NLM ID

0364456

Subset

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Arsenic-induced NFkappaB transactivation through Erks- and JNKs-dependent pathways in mouse epidermal JB6 cells.

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