Lead-induced apoptosis in PC 12 cells: involvement of p53, Bcl-2 family and caspase-3.
It has been reported that lead could induce apoptosis in a variety of cell types. Although mitochondrion is regarded as the most pertinent pathway in mediating apoptosis, the exact mechanisms of lead-induced apoptosis are still largely unknown. Furthermore, there is little information about expressions and regulations of Bax, Bcl-2, and p53 in lead-induced apoptosis, which are critical regulators of mitochondrial stability. The present study was undertaken to determine whether lead could induce DNA damage and apoptosis in PC 12 cells, and the involvement of Bax, Bcl-2, p53, and caspase-3 in this process. The results showed that lead could induce DNA damage and apoptosis in PC 12 cells, accompanying with upregulation of Bax and downregulation of Bcl-2. Additionally, the expression of p53 increased, and caspase-3 was activated. Therefore, it suggests that lead can induce activation of p53 by DNA damage, which may lead to imbalance of Bax/Bcl-2 and mitochondrial dysfunction. Subsequently, after activation of caspase-3, lead-induced apoptosis occurres.
Xu
Jin
J
Department of Biochemistry and Molecular biology, School of Medicine, Zhejiang University, Hangzhou 310031, PR China.
Ji
Lin-Dan
LD
Xu
Li-Hong
LH
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D004249:DNA Damage; D020287:In Situ Nick-End Labeling; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D009942:Organometallic Compounds / Q000633:toxicity*; D016716:PC12 Cells; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051381:Rats; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D009942:Organometallic Compounds; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; C008261:lead acetate