Mutant nicastrin protein can induce the cytochrome c release and the Bax expression.
This study investigated whether nicastrin can induce apoptotic cell death in SK-N-MC cells. MTT assays revealed the transfected cells expressing mutant nicastrin, compared with those expressing wild nicastrin or the control vector, showing significantly increased cell death. The mutant nicastrin transfectants were also observed to induce cytosolic cytochrome c release from the mitochondria, and Bax protein expression in response, to increased cell death. These observations suggested that nicastrin, as well as the APP and PS proteins, were also involved in the upregulated Bax mediated neuroblastoma cell death and the release of cytochrome c in the neuroblastoma.
Hwang
Dae Y
DY
Division of Laboratory Animal Resources, Korea FDA, National Institute of Toxicological Research, Seoul, Korea. dyhwang@kfda.go.kr
Kim
Yong K
YK
Lim
Chul J
CJ
Cho
Jung S
JS
D053829:Amyloid Precursor Protein Secretases; D015153:Blotting, Western / Q000379:methods; D016923:Cell Death / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology; D045304:Cytochromes c / Q000378:metabolism*; D004252:DNA Mutational Analysis / Q000379:methods; D005786:Gene Expression Regulation; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D008928:Mitochondria / Q000378:metabolism; D016297:Mutagenesis, Site-Directed / Q000502:physiology; D009154:Mutation; D009447:Neuroblastoma; D016133:Polymerase Chain Reaction / Q000379:methods; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D013778:Tetrazolium Salts; D013844:Thiazoles; D014162:Transfection / Q000379:methods; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D008562:Membrane Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D013778:Tetrazolium Salts; D013844:Thiazoles; D051028:bcl-2-Associated X Protein; C413604:nicastrin protein; D045304:Cytochromes c; D053829:Amyloid Precursor Protein Secretases; C022616:thiazolyl blue