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

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.

• Authors: C Huang, J Li, M Ding, L Wang, X Shi, V Castranova, V Vallyathan, G Ju, M Costa
• Journal: Molecular and cellular biochemistry (Mol Cell Biochem) Vol. 222 Issue 1-2 Pg. 29-34 (Jun 2001) ISSN: 0300-8177 [Print] Netherlands
• PMID: 11678607 (Publication Type: Journal Article)

Chemical References

• 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

Topics

• 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)