Jump to main content
US EPA
United States Environmental Protection Agency
Search
Search
Main menu
Environmental Topics
Laws & Regulations
About EPA
Health & Environmental Research Online (HERO)
Contact Us
Print
Feedback
Export to File
Search:
This record has one attached file:
Add More Files
Attach File(s):
Display Name for File*:
Save
Citation
Tags
HERO ID
1070343
Reference Type
Journal Article
Title
Effects of arsenite and UVA-1 radiation on calcineurin signaling
Author(s)
Musson, REA; Mullenders, LHF; Smit, NPM
Year
2012
Is Peer Reviewed?
1
Journal
Mutation Research
ISSN:
0027-5107
EISSN:
1873-135X
Volume
735
Issue
1-2
Page Numbers
32-38
Language
English
PMID
22564430
DOI
10.1016/j.mrfmmm.2012.04.007
Web of Science Id
WOS:000306723000004
Abstract
Calcineurin is a Ca(2+)-dependent serine/threonine phosphatase and the target of the immunosuppressive drugs cyclosporin and tacrolimus, which are used in transplant recipients to prevent rejection. Unfortunately, the therapeutic use of this drugs is complicated by a high incidence of skin malignancy, which has set off a number of studies into the role of calcineurin signaling in skin, particularly with respect to cell cycle control and DNA repair. Both UVA1 radiation and arsenic species are known to promote skin cancer development via production of reactive oxygen species. In light of the well-documented sensitivity of calcineurin to oxidative stress, we examined and compared the effects of UVA1 and arsenite on calcineurin signaling. In this paper, we show that physiologically relevant doses of UVA1 radiation and low micromolar concentrations of arsenite strongly inhibit calcineurin phosphatase activity in Jurkat and skin cells and decrease NFAT nuclear translocation in Jurkat cells. The effects on calcineurin signaling could be partly prevented by inhibition of NADPH oxidase in Jurkat cells or increased dismutation of superoxide in Jurkat and skin cells. In addition, both UVA1 and arsenite decreased NF-κB activity, although at lower concentrations, arsenite enhanced NF-κB activity. These data indicate that UVA1 and arsenite affect a signal transduction route of growingly acknowledged importance in skin and that calcineurin may serve as a potential link between ROS exposure and impaired tumor suppression.
Keywords
Calcineurin; Reactive oxygen species; UVA radiation; Arsenite; NFAT; Skin carcinogenesis
Tags
IRIS
•
Arsenic Hazard ID
1. Initial Lit Search
PubMed
WOS
WOS
Excluded
Non Peer Reviewed
2. Lit Search Updates through Oct 2015
WOS
Initial Filter
Non Peer Reviewed
3. Initial Filter through Oct 2015
Non Peer-Reviewed
7. Other Studies through Oct 2015
MOA
•
Arsenic (Inorganic)
1. Literature
PubMed
Web of Science
Lit search updates through Oct 2015
2. Initial Filter
Non peer-reviewed
3. Hazard ID Screening
Other potentially supporting studies
4. Adverse Outcome Pathways/Networks Screening
Relevant
•
Arsenic MOA
4. Adverse Outcome Pathways
Other MOA
5. Health Effect
Skin Diseases
Cancer
1. MOA Literature Screening
Health Effect Screening
•
Arsenic Susceptibility
Life Stages Citation Mapping
20%-25%
Home
Learn about HERO
Using HERO
Search HERO
Projects in HERO
Risk Assessment
Transparency & Integrity