Arsenic Induces Human Keratinocyte Apoptosis by the FAS/FAS Ligand Pathway, Which Correlates with Alterations in Nuclear Factor-κB and Activator Protein-1 Activity
Journal
Journal of Investigative Dermatology
Journal Volume
122
Journal Issue
1
Pages
125-129
Date Issued
2004
Author(s)
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-κB (NF-κB) 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-κB and AP-1 activity, we exposed cultured human foreskin keratinocytes to different concentrations of sodium arsenite. At lower concentrations (?1 μM), arsenic induced keratinocyte proliferation and enhanced both NF-κB and AP-1 activity. At higher concentrations (?5 μM), arsenic induced keratinocyte apoptosis by the Fas/Fas ligand (FasL) pathway. At apoptosis induction concentrations, NF-κB activity was not enhanced; however, AP-1 activity was further enhanced. These results indicated that upregulation of NF-κB 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
Cytotoxicity; Death receptor; Sodium arsenite; Transcription factor
SDGs
Other Subjects
arsenic; arsenite sodium; Fas antigen; Fas ligand; immunoglobulin enhancer binding protein; transcription factor AP 1; apoptosis; article; cell culture; cell proliferation; concentration (parameters); controlled study; correlation analysis; exposure; human; human cell; keratinocyte; prepuce; priority journal; protein analysis; upregulation
Publisher
Blackwell Publishing Inc.
Type
journal article