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KMID : 1140120100150040326
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Cancer Prevention Research
2010 Volume.15 No. 4 p.326 ~ p.332
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A Study on Apoptosis Regulation by Decreased Expression Level of Endogenous Thioredoxin 1
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Kim Hye-Lim
Koedrith Preeyaporn
Seo Young-Rok
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Abstract
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Thioredoxin 1 (Trx1) is well known as an important redox factor to protect cells from oxidative stress. Recently, Trx1 is being suggested as redox-sensitive molecular target for cancer therapy. Apoptosis is able to be induced by various stimuli including oxidative stress and DNA damage. In this study, we investigated the suppression of Trx1 on apoptosis enhancement under the exposure of ethyl methanesulfonate (EMS) as one of the environmental mutagens. We constructed stable Trx1 knockdown cells from human colon-derived RKO cell line using shRNA system, showing the accumulation of endogenous ROS level. Furthermore, we found significantly enhanced apoptosis in the EMS treated-Trx1 shRNA cells relative to wild type, as evidenced by increase in apoptotic fraction and expression levels of caspase 3. These results imply that Trx1 has crucial effects on severe apoptosis induced by environmental mutagen generated DNA damage through the regulation of redox status as a ROS scavenger. Therefore, we suggest the role of Trx1 as a key component of redox regulation in EMS-induced toxicity. This may represent Trx1 activity as subcellular biomarker of redox imbalance under environmental exposure to toxic compounds.
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KEYWORD
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Thioredoxin 1, Environmental mutagen, Apoptosis, ROS, DNA damage
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