Mechanism of apoptosis induced by copper in PC12 cells.
Copper, an essential trace element, induces apoptosis in mammalian cells. However, the precise mechanism of copper-induced apoptosis is still unclear. In this study, to determine the apoptotic pathway initiated by copper treatment, apoptotic factors such as Bax, Bad and Bcl-2, and the caspase family in PC12 cells treated with copper were measured by Western blot and RT-PCR analyses. The expression of Bax, Bad, cytochrome c and caspases 3 and 9 were increased by copper treatment. From these results, two pathways for copper-induced apoptosis were suggested. At first, an increase of Bax induces the release of cytochrome c from the mitochondria into the cytoplasm owing to binding to apoptotic activating caspase 9 leading to the activation of caspases 3. In the other pathway an increase of Bax and reactive oxygen species activates the release of AIF from the mitochondria. The AIF induces apoptosis via a caspase-independent pathway.
Kawakami
Masaki
M
Environmental Remediation and Analysis, Division of Environmental Development, Graduate School of Environmental Science, Hokkaido University, Japan.
Inagawa
Rieko
R
Hosokawa
Toshiyuki
T
Saito
Takeshi
T
Kurasaki
Masaaki
M
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D002467:Cell Nucleus / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D004396:Coloring Agents; D003300:Copper / Q000378:metabolism / Q000633:toxicity*; D045304:Cytochromes c / Q000378:metabolism; D004247:DNA / Q000235:genetics; D053938:DNA Fragmentation / Q000187:drug effects; D004587:Electrophoresis, Agar Gel; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D016716:PC12 Cells; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014343:Trypan Blue; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051025:bcl-Associated Death Protein / Q000378:metabolism
D004396:Coloring Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; D003300:Copper; D045304:Cytochromes c; D004247:DNA; D007770:L-Lactate Dehydrogenase; D020169:Caspases; D014343:Trypan Blue