Skip Navigation



ToxSci Advance Access published online on August 19, 2004
Toxicological Sciences, doi:10.1093/toxsci/kfh256
Toxicological Sciences © Society of Toxicology 2004; all rights reserved
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
82/1/183    most recent
kfh256v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Treichel, J. L.
Right arrow Articles by Burke, J. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Treichel, J. L.
Right arrow Articles by Burke, J. M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Received April 12, 2004
Accepted August 10, 2004

In Vitro Toxicology

Antioxidants and Ocular Cell Type Differences in Cytoprotection from Formic Acid Toxicity in Vitro

Jaime L. Treichel 1, Michele M. Henry 2, Christine M. B. Skumatz 2, Janis T. Eells , Janice M. Burke 3*

1 Departments of Pharmacology & Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226
2 Department of Ophthalmology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226
3 Departments of Pharmacology & Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226; Department of Ophthalmology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226

* To whom correspondence should be addressed. E-mail: jburke{at}mcw.edu.


  Abstract

Retinal photoreceptors and retinal pigment epithelial (RPE) cells are among the cell types that are sensitive to poisoning with methanol and its toxic metabolite formic acid. When exposed to formic acid in vitro, cultured cell lines from photoreceptors (661W) and the RPE (ARPE-19) were previously shown to accumulate similar levels of formate, but cytotoxic effects are greater in 661W cells. Here catalase and glutathione were analyzed in the two retinal cell lines to determine whether differences in these antioxidant systems contributed to cell-type specific differences in cytotoxicity. Cells were exposed to formic acid (pH 6.8) in the culture medium in the presence or absence of a catalase activity inhibitor, 3-amino-1,2,4-triazole (AT), or a glutathione synthesis inhibitor, buthionine L-sulfoximine (BSO). Catalase protein, catalase enzyme activity, glutathione, glutathione peroxidase activity, cellular ATP, and cytotoxicity were analyzed. Compared to ARPE-19, 661W cells show lower antioxidant levels: 50% less glutathione, glutathione peroxidase and catalase protein, and 90% less catalase enzyme activity. In both cell types, formic acid treatment produced decreases in glutathione and glutathione peroxidase, and glutathione synthesis inhibition with BSO produced greater ATP depletion and cytotoxicity tha n formic acid treatment alone. In contrast, formate exposure produced decreases in catalase protein and activity in 661W cells, but increases in activity in ARPE-19. Treatment with the catalase inhibitor AT increased the formate sensitivity only of the ARPE-19 cells. ARPE-19 cells therefore may be less susceptible to formate toxicity due to higher levels of antioxidants, especially catalase, which increases on formate treatment and which has a significant cytoprotective effect for the RPE cell line.

Keywords: formate; methanol; photoreceptors; glutathione; catalase.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 IOVSHome page
X. Zhang, J. Zhou, A. F. Fernandes, J. R. Sparrow, P. Pereira, A. Taylor, and F. Shang
The Proteasome: A Target of Oxidative Damage in Cultured Human Retina Pigment Epithelial Cells
Invest. Ophthalmol. Vis. Sci., August 1, 2008; 49(8): 3622 - 3630.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.