Paraquat-induced oxidative stress and dysfunction of cellular redox systems including antioxidative defense enzymes glutathione peroxidase and thioredoxin reductase
| Autor: | Masashi Takizawa, Yoshiko Tampo, Masanori Yonaha, Kumiko Komori |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
inorganic chemicals
Paraquat Thioredoxin-Disulfide Reductase GPX3 Cell Survival Swine Thioredoxin reductase Glutathione reductase Biology Toxicology Cell Line chemistry.chemical_compound Selenium Glutaredoxin Animals chemistry.chemical_classification Glutathione Peroxidase Thiomalates Dose-Response Relationship Drug Herbicides Glutathione peroxidase Glyceraldehyde-3-Phosphate Dehydrogenases General Medicine Glutathione Hydrogen Peroxide Peroxiredoxins Molecular biology Drug Combinations Oxidative Stress Biochemistry chemistry Peroxidases Endothelium Vascular Thioredoxin |
| Zdroj: | Toxicology in vitro : an international journal published in association with BIBRA. 21(3) |
| ISSN: | 0887-2333 |
| Popis: | We examined if paraquat-induced oxidative stress and cytotoxicity in pulmonary microvascular endothelial cells are associated with cellular redox systems such as the glutathione system and the thioredoxin system. Loss of viability, accompanied by marked decreases in glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and thioredoxin reductase activities, occurred 48 h after exposure to 1mM paraquat. These changes were preceded by an increased production of hydrogen peroxide after the decrease in glutathione peroxidase activity. Glutaredoxin activity was not decreased even after exposure to paraquat for 48 h, whereas thioredoxin activity was slightly decreased at 48 h. Unexpectedly, the activity of peroxiredoxin, a non-selenoenzyme, was almost completely lost at 24h. Loss of GAPDH activity and viability was notably aggravated by mercaptosuccinate. Selenium supplementation suppressed the loss of activities of glutathione peroxidase and thioredoxin reductase and alleviated paraquat-induced cytotoxicity. An in vitro experiment demonstrated that GAPDH was highly susceptible to reactive oxygen species generated in the xanthine-xanthine oxidase system, whereas thioredoxin reductase was considerably resistant. Taken together, the results suggest that the reduced regenerative ability of oxidatively damaged proteins including GAPDH due to the inactivation of thioredoxin reductase and glutathione peroxidase by paraquat may contribute to increasing oxidative stress, leading to cell death. |
| Databáze: | OpenAIRE |
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