Induction of apoptotic cell death by a p53-independent pathway in neuronal SK-N-MC cells after treatment with 2,2',5,5'-tetrachlorobiphenyl.
Apoptotic cell death is an active process, which is a critical feature of the regulated development of multicellular organisms. Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants, some of which may be neurotoxic. This study investigates the 2,2', 5,5'-tetrachlorobiphenyl (PCB 52) induced apoptosis in human neuronal SK-N-MC cells, and the role of p53 in this response. Upon treatments with PCB 52, time- and concentration-dependent inhibition of the cell viability was observed. PCB 52 also caused apoptosis, as measured by cell morphology and DNA fragmentation. The capability of PCB 52 to induce apoptosis was associated with the proteolytic cleavage of specific target proteins, such as poly(ADP-ribose) polymerase (PARP) and beta-catenin proteins, suggesting the possible involvement of caspases. In general, DNA-damaging agents induce accumulation of the tumor suppressor protein p53, leading cells to either growth arrest in G1, or apoptosis. However, our data showed that both p53 and Bcl-2 protein levels were decreased in a time-dependent manner during apoptosis after exposure to PCB 52. These results suggest that PCB 52 induced a p53-independent apoptosis in these cells.
Hwang
S G
SG
Department of Biochemistry and Health Sciences, College of Natural Sciences, Changwon National University, Changwon, 641-773, Kyungnam, South Korea.
Lee
H C
HC
Lee
D W
DW
Kim
Y S
YS
Joo
W H
WH
Cho
Y K
YK
Moon
J Y
JY
D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D020169:Caspases / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D009447:Neuroblastoma; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D015534:Trans-Activators; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; D051176:beta Catenin; C009407:2,5,2',5'-tetrachlorobiphenyl; D011078:Polychlorinated Biphenyls; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases