Journal article
Inactivation of Primary Antioxidant Enzymes in Mouse Keratinocytes by Photodynamically Generated Singlet Oxygen
Antioxidants & redox signaling, Vol.8(7-8), pp.1307-1314
07/2006
DOI: 10.1089/ars.2006.8.1307
PMID: 16910778
Abstract
Cellular antioxidant enzymes protect against damage caused by exposure to endogenous or exogenous prooxidants. Singlet oxygen ((1)O(2)) is a reactive form of oxygen that can be produced in vivo either in normal and pathophysiologic conditions or by photosensitizing chemicals, as during photodynamic treatment. We hypothesized that photodynamically generated (1)O(2) would decrease the enzymatic activities of cellular antioxidants. To test this hypothesis, we treated cultured mouse epidermal keratinocytes with the photosensitizer Photofrin plus visible light to produce (1)O(2), and then measured CuZnSOD, MnSOD, and catalase activities with both ingel and spectrophotometric enzyme activity assays. Our results demonstrated that the enzymatic activities of cellular CuZnSOD, MnSOD, and catalase were significantly decreased after keratinocytes were treated with Photofrin plus visible light. By contrast, the enzymatic activities of cellular CuZnSOD, MnSOD, and catalase were unaffected in control cells treated with Photofrin only or visible light only. Despite the decreased levels of enzymatic activities, the protein levels of all three primary antioxidant enzymes remained constant after photodynamic treatment, as determined by Western blotting. L-Histidine, a (1)O(2) quencher, protected against the inactivation of cellular CuZnSOD, MnSOD, and catalase enzymes induced by photodynamically generated (1)O(2). The conclusion from these experiments is that the primary cellular antioxidant enzymes CuZnSOD, MnSOD, and catalase can be inactivated by photodynamically generated (1)O(2) in nucleated mammalian cells. These findings may be useful in the future development of antineoplastic adjuvant therapies that use photodynamic generation of (1)O(2) to inactivate antioxidant defenses with a goal of sensitizing tumor cells to prooxidant-generating drugs.
Details
- Title: Subtitle
- Inactivation of Primary Antioxidant Enzymes in Mouse Keratinocytes by Photodynamically Generated Singlet Oxygen
- Creators
- Jun Luo - Free Radical and Radiation Biology Graduate Program, Department of Radiation Oncology, The University of Iowa, Iowa City, IowaLing Li - Free Radical and Radiation Biology Graduate Program, Department of Radiation Oncology, The University of Iowa, Iowa City, IowaYuping Zhang - Free Radical and Radiation Biology Graduate Program, Department of Radiation Oncology, The University of Iowa, Iowa City, IowaDouglas R Spitz - Free Radical and Radiation Biology Graduate Program, Department of Radiation Oncology, The University of Iowa, Iowa City, IowaGarry R Buettner - Free Radical and Radiation Biology Graduate Program, Department of Radiation Oncology, The University of Iowa, Iowa City, IowaLarry W Oberley - Free Radical and Radiation Biology Graduate Program, Department of Radiation Oncology, The University of Iowa, Iowa City, IowaFrederick E Domann - Free Radical and Radiation Biology Graduate Program, Department of Radiation Oncology, The University of Iowa, Iowa City, Iowa
- Resource Type
- Journal article
- Publication Details
- Antioxidants & redox signaling, Vol.8(7-8), pp.1307-1314
- DOI
- 10.1089/ars.2006.8.1307
- PMID
- 16910778
- ISSN
- 1523-0864
- eISSN
- 1557-7716
- Language
- English
- Date published
- 07/2006
- Academic Unit
- Pathology; Surgery; Radiation Oncology; Obstetrics and Gynecology
- Record Identifier
- 9984047682602771
Metrics
8 Record Views