Effect of glutathione depletion on apoptosis induced by thiram in Chinese hamster fibroblasts
| Autor: | Maria Szumiło, E. Grosicka, Iwonna Rahden-Staroń, B. Sadurska, P. Łazarczyk, J. Niderla-Bielińska, Tomasz Grzela |
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| Rok vydání: | 2005 |
| Předmět: |
Thiram
Cell Survival Immunology Hamster Apoptosis medicine.disease_cause Chinese hamster Cell Line Lethal Dose 50 chemistry.chemical_compound Cricetinae medicine TBARS Animals Immunology and Allergy Sulfhydryl Compounds Caspase Pharmacology Dose-Response Relationship Drug biology Proteins Glutathione Fibroblasts biology.organism_classification Fungicides Industrial Oxidative Stress chemistry Biochemistry biology.protein Lipid Peroxidation Oxidation-Reduction Oxidative stress |
| Zdroj: | International Immunopharmacology. 5:1945-1956 |
| ISSN: | 1567-5769 |
| Popis: | Fungicide thiram, which is also known as an inducer of allergic contact dermatitis (ACD), was used as a model compound of thiuram chemicals, and its cellular effects were investigated in cultured Chinese hamster V79 cells. The level of intracellular reduced glutathione (GSH), protein sulfhydryl (PSH) groups, protein carbonyls (PC), membrane lipid peroxidation reflected by enhanced thiobarbituric acid reactive substrates (TBARS) production, as well as apoptotic effect were determined. The apoptosis induction was determined by assessing DNA fragmentation by TUNEL, annexin V binding, and caspases activation assays, using fluorescent microscope or flow cytometry, respectively. The concentrations of thiram required to induce cellular GSH depletion (by 40–50%), protein, and membrane lipid peroxidation (2-fold, and 1.7-fold, respectively), as well as to induce apoptosis in V79 Chinese hamster fibroblasts without causing necrosis through cytotoxic effects were between 50–100 μM. To investigate the role of decreased GSH content in the toxicity of thiram, GSH level was modified prior to exposure. Pretreatment of V79 cells with N -acetyl- l -cysteine (NAC), a GSH biosynthesis precursor, prevented GSH decrease, PC and TBARS production, as well as caspases activation induced by thiram exposure. On the other hand, thiram effects were enhanced by the previous depletion of cellular GSH by l -buthionine-(S,R)-sulfoximine (BSO). |
| Databáze: | OpenAIRE |
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