Abstract
In this study, BRL 3A cells were treated with different Cd concentrations (0, 10, 20, and 40 μmol/L) for 12 h and preincubated with or without N-acetyl-L-cysteine (NAC) (2 mmol/L) for 30 min, and cells were treated with Cd (0 and 20 μmol/L), pretreated with p38 inhibitor (SB203580), JNK (c-Jun NH2-terminal kinases) inhibitor (SP600125), and extracellular signal-regulated kinase (ERK) inhibitor (U0126) for 30 min, and then treated with 20 μmol/L Cd for 12 h. Cd decreased cell viability, SOD, and GSH-Px activity in a concentration-dependent manner. Increased MDA level, ROS generation, nuclear condensation, shrinkage, and fragmentation in cell morphology were inhibited by NAC. Cd-induced apoptosis was attenuated by pretreatment with SB203580, SP600125, and U0126. The results of western blot showed that NAC preincubation affected Cd-activated MAPK pathways, p38 and ERK phosphorylation. Cd treatment elevated the mRNA levels of Bax and decreased the mRNA levels of Bcl-2, respectively. The same effect was found in their protein expression levels. These results suggest that oxidative stress and MAPK pathways participate in Cd-induced apoptosis and that the balance between pro- and antiapoptotic genes (Bax and Bcl-2) is important in Cd-induced apoptosis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylcysteine / pharmacology
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Animals
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Anthracenes / pharmacology
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Apoptosis / drug effects*
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Butadienes / pharmacology
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Cadmium / toxicity*
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Cell Line
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Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Glutathione Peroxidase / metabolism
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Imidazoles / pharmacology
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JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors
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JNK Mitogen-Activated Protein Kinases / metabolism
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Malondialdehyde / metabolism
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Mitogen-Activated Protein Kinases / metabolism*
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Nitriles / pharmacology
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Oxidative Stress / drug effects*
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Phosphorylation
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Protein Kinase Inhibitors / pharmacology
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Pyridines / pharmacology
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Rats
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Reactive Oxygen Species / metabolism
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Signal Transduction / drug effects
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Superoxide Dismutase / metabolism
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p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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Anthracenes
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Butadienes
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Imidazoles
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Nitriles
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Protein Kinase Inhibitors
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Pyridines
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Reactive Oxygen Species
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U 0126
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Cadmium
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pyrazolanthrone
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Malondialdehyde
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Glutathione Peroxidase
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Superoxide Dismutase
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Extracellular Signal-Regulated MAP Kinases
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases
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SB 203580
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Acetylcysteine