Arsenic Induces Human Keratinocyte Apoptosis by the Fas/Fas Ligand Pathway, Which Correlates with Alterations in Nuclear Factor-Kappa B and Activator Protein-1 Activity
Resource
JOURNAL OF INVESTIGATIVE DERMATOLOGY v.122 n.1 pp.125-129
Journal
JOURNAL OF INVESTIGATIVE DERMATOLOGY
Journal Volume
v.122
Journal Issue
n.1
Pages
125-129
Date Issued
2004
Date
2004
Author(s)
CHANG, KEE-LUNG
YU, CHIA-LI
Abstract
Epidemiologic studies demonstrated that long-term exposure to arsenic induces arsenical skin cancers, including Bowen's disease. Immunohistochemically, Bowen's disease shows proliferating and apoptotic characteristics. The transcription factors nuclear factor-kappaB (NF- kappaB) and activator protein-1 (AP-1) functionally regulate cell proliferation, transformation, and apoptosis. To investigate the mechanism of arsenic-induced apoptosis and related alterations in NF-kappaB and AP- 1 activity, we exposed cultured human foreskin keratinocytes to different concentrations of sodium arsenite. At lower concentrations ( less than or equal to1 muM), arsenic induced keratinocyte proliferation and enhanced both NF-kappaB and AP-1 activity. At higher concentrations (greater than or equal to5 muM), arsenic induced keratinocyte apoptosis by the Fas/Fas ligand (FasL) pathway. At apoptosis induction concentrations, NF- kappaB activity was not enhanced; however, AP-1 activity was further enhanced. These results indicated that upregulation of NF-kappaB at lower arsenic concentrations was correlated with keratinocyte proliferation. In contrast , higher concentrations of arsenic enhanced AP-1 and induced Fas/FasL - associated apoptosis. The concentration-dependent arsenic effects on transcription factors activity can help to clarify the mechanisms in arsenic-induced proliferation and apoptosis in keratinocytes.
Subjects
sodium arsenite
transcription factor
cytotoxicity
death receptor
SDGs