Arsenic-induced NFkappaB transactivation through Erks- and JNKs-dependent pathways in mouse epidermal JB6 cells.
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.
Huang
C
C
Nelson Institute of Environmental Medicine, New York University School of Medicine, NY 10016, USA.
Li
J
J
Ding
M
M
Wang
L
L
Shi
X
X
Castranova
V
V
Vallyathan
V
V
Ju
G
G
Costa
M
M
D000818:Animals; D001149:Arsenates / Q000494:pharmacology; D001151:Arsenic / Q000494:pharmacology*; D018053:Arsenites / Q000494:pharmacology; D002460:Cell Line; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects* / Q000201:enzymology; D005419:Flavonoids / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000096:biosynthesis*; D015533:Transcriptional Activation / Q000187:drug effects*
D001149:Arsenates; D018053:Arsenites; D004791:Enzyme Inhibitors; D005419:Flavonoids; D016328:NF-kappa B; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D001151:Arsenic; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one