title: Thioredoxin-1 contributes to protection against DON-induced oxidative damage in HepG2 cells.
abstract: Leucocytes are susceptible to the toxic effects of deoxynivalenol (DON), which is a trichothecene mycotoxin produced by a number of fungi including Fusarium species. One mechanism of action is mediated by reactive oxygen species (ROS). The liver is an important target for toxicity caused by foreign compounds including mycotoxins. On the other hand, little is known about the influence of the redox state on hepatocytes treated with DON. The present study investigated the effect of DON on the cytosolic redox state and antioxidative system in the human hepatoma cell line HepG2. The cell viability of human monocyte cell line THP-1 or leukemia cell line KU812 treated with 2.5 and 5 μmol/l DON were significantly reduced. However, HepG2 cells showed no toxic effects under the same conditions and did not exhibit an increased oxidative state. Further experiments showed that thioredoxin-1 (Trx-1) protein levels but not glutathione increased in the cells treated with 10 μmol/l DON. In addition, the enhancement of Trx-1 content was repressed by antioxidants. These results suggest that DON-induced accumulation of Trx-1 in HepG2 cells plays one of the key roles in protection against cytotoxicity caused by DON and that the mechanism may be mediated by the antioxidant properties of Trx-1.
authors.affiliation: Division of Microbiology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo, 158-8501, Japan. sugiyama@nihs.go.jp
authors.forename: Kei-Ichi
authors.initials: K
authors.lastname: Sugiyama
authors.forename: Mawo
authors.initials: M
authors.lastname: Kinoshita
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Kamata
authors.forename: Yuji
authors.initials: Y
authors.lastname: Minai
authors.forename: Fumito
authors.initials: F
authors.lastname: Tani
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Sugita-Konishi
mesh_terms: D000975:Antioxidants / Q000378:metabolism* / Q000494:pharmacology; D002460:Cell Line; D056945:Hep G2 Cells / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects*; D006801:Humans; D007962:Leukocytes / Q000187:drug effects*; D009183:Mycotoxins / Q000494:pharmacology / Q000633:toxicity; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism / Q000494:pharmacology; D013879:Thioredoxins / Q000378:metabolism* / Q000494:pharmacology; D014255:Trichothecenes / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity*
chemical_list: D000975:Antioxidants; D009183:Mycotoxins; D017382:Reactive Oxygen Species; D014255:Trichothecenes; D013879:Thioredoxins; C007262:deoxynivalenol