1. Oxidative stress and mitogen-activated protein kinase pathways involved in cadmium-induced BRL 3A cell apoptosis.
- Author
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Yiran Z, Chenyang J, Jiajing W, Yan Y, Jianhong G, Jianchun B, Xuezhong L, and Zongping L
- Subjects
- Acetylcysteine pharmacology, Animals, Anthracenes pharmacology, Butadienes pharmacology, Cell Line, Extracellular Signal-Regulated MAP Kinases antagonists & inhibitors, Extracellular Signal-Regulated MAP Kinases metabolism, Glutathione Peroxidase metabolism, Imidazoles pharmacology, JNK Mitogen-Activated Protein Kinases antagonists & inhibitors, JNK Mitogen-Activated Protein Kinases metabolism, Malondialdehyde metabolism, Nitriles pharmacology, Phosphorylation, Protein Kinase Inhibitors pharmacology, Pyridines pharmacology, Rats, Reactive Oxygen Species metabolism, Signal Transduction drug effects, Superoxide Dismutase metabolism, p38 Mitogen-Activated Protein Kinases antagonists & inhibitors, p38 Mitogen-Activated Protein Kinases metabolism, Apoptosis drug effects, Cadmium toxicity, Mitogen-Activated Protein Kinases metabolism, Oxidative Stress drug effects
- 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.
- Published
- 2013
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