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Enhanced ROS production and redox signaling with combined arsenite and UVA exposures
Author(s) -
Cooper Karen L,
Liu Ke Jian,
Hudson Laurie G
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.706.2
Subject(s) - arsenite , reactive oxygen species , nadph oxidase , oxidative stress , chemistry , p38 mitogen activated protein kinases , heme oxygenase , superoxide dismutase , microbiology and biotechnology , biochemistry , arsenic , signal transduction , heme , biology , enzyme , mapk/erk pathway , organic chemistry
Solar ultraviolet radiation (UVR) is the major etiological factor in skin carcinogenesis. In vivo studies demonstrate that mice exposed to arsenic and UVR exhibit significantly more tumors and oxidative DNA damage than animals treated with either agent alone. Interactions between arsenite and UVR in the production of reactive oxygen species (ROS) and stress‐associated signaling may provide a basis for the enhanced carcinogenicity. Here keratinocytes were pretreated with arsenite (3 µM) then exposed to UVA (10 kJ/m 2 ). Exposure to UVA following arsenite pretreatment enhanced ROS production, p38 MAP kinase activation and induction of heme oxygenase‐1, when compared to either stimulus alone. Arsenite exposure resulted in pronounced and persistent NADPH oxidase (NOX) activation whereas UVA activation was rapid and transient. Inhibition of NOX decreased ROS production in arsenite treated cells but had little impact on UVA exposed cells. Furthermore, arsenite‐, but not UVA‐, induced p38 activation and HO‐1 expression were dependent upon NOX activity. These findings indicate differences in mechanisms of ROS production by arsenite and UVA that may provide an underlying basis for the observed enhancement of redox‐related cellular responses. Work supported by NIH R01 ES012938, NIH AR 42989, NIEHS P30‐ES‐012‐72, and EPA STAR Fellowship FP‐91650201‐1.