Journal article
Superoxide generation in v‐Ha‐ras–transduced human keratinocyte HaCaT cells
Molecular carcinogenesis, Vol.26(3), pp.180-188
11/1999
DOI: 10.1002/(SICI)1098-2744(199911)26:3<180::AID-MC7>3.3.CO;2-W
PMID: 10559793
Abstract
The oncogenic ras protein controls signal‐transduction pathways that are critical for cell proliferation and tumorigenesis. Here, we demonstrate that v‐Ha‐ras–transduced human keratinocyte HaCaT cells produced significantly larger amounts of superoxide than did control cell lines. The superoxide generation was mediated by the transduced ras protein, because superoxide generation was modified by an inhibitor, lovastatin, that inhibits ras farnesylation during ras protein maturation. Superoxide generation was also inhibited by diphenylene iodonium, an inhibitor of flavoproteins, including NADPH oxidase, but not by rotenone, an inhibitor of the respiratory chain of the mitochondria. Those observations suggested that a phagocytic‐like NADPH oxidase exists in keratinocytes that could be activated by the dominant activated v‐Ha‐ras and produce superoxide. Overexpression of manganese‐containing superoxide dismutase and copper and zinc–containing superoxide dismutase cDNA via adenovirus infection also attenuated superoxide generation. Previous work has demonstrated that extracellular superoxide dismutase (SOD) can lower superoxide generation; this is the first report that intracellular SOD could also modify the amount of superoxide production from the cells. This report implies that superoxide radical may act as a second messenger molecule of oncogenic ras.
Details
- Title: Subtitle
- Superoxide generation in v‐Ha‐ras–transduced human keratinocyte HaCaT cells
- Creators
- Ji‐Qin Yang - University of IowaShijun LiFrederick E Domann - University of Iowa, Radiation OncologyGarry R Buettner - University of Iowa, Radiation OncologyLarry W Oberley
- Resource Type
- Journal article
- Publication Details
- Molecular carcinogenesis, Vol.26(3), pp.180-188
- DOI
- 10.1002/(SICI)1098-2744(199911)26:3<180::AID-MC7>3.3.CO;2-W
- PMID
- 10559793
- ISSN
- 0899-1987
- eISSN
- 1098-2744
- Language
- English
- Date published
- 11/1999
- Academic Unit
- Pathology; Surgery; Radiation Oncology
- Record Identifier
- 9984047884002771
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