N141I mutant presenilin-2 gene enhances neuronal cell death and decreases bcl-2 expression.

Abstract	A missense mutation (N1411) in Presenilin-2 (PS-2) gene is associated with early-onset familial Alzheimer's disease. In this study, SK-N-SH human neuroblastoma cells were transfected with wild-type and mutant PS-2 gene to examine presenilin-2 effects on apoptosis. Serum deprivation resulted in enhanced apoptosis in mutant PS-2 comparing with wild-type PS-2. Similarly, mutant PS-2 induced lactate dehydrogenase release to greater extent than wild-type PS-2. Time course experiment demonstrated that the increase in caspase-3-like activity was more pronounced and accelerated in mutant PS-2, compared to wild-type PS-2. While a significant decrease in bcl-2, an anti-apoptotic molecule, occurred in the cells overexpressing mutant PS-2, no significant change was observed in bax, a pro-apoptotic molecule, as compared with the cells overexpressing wild-type PS-2. Our study demonstrated that mutant PS-2 induces apoptosis accompanied by increased caspase-3-like activity and decreased bcl-2 expression in neuronal cells after serum-deprivation.
Authors	Masaki Mori, Hironori Nakagami, Ryuichi Morishita, Noriaki Mitsuda, Kei Yamamoto, Shin-ichi Yoshimura, Nobutaka Ohkubo, Naoyuki Sato, Toshio Ogihara, Yasufumi Kaneda
Journal	Life sciences (Life Sci) Vol. 70 Issue 21 Pg. 2567-80 (Apr 21 2002) ISSN: 0024-3205 [Print] Netherlands
PMID	12173418 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	BAX protein, human Culture Media, Serum-Free DNA, Complementary Membrane Proteins Nerve Tissue Proteins PSEN2 protein, human Presenilin-2 Proto-Oncogene Proteins Proto-Oncogene Proteins c-bcl-2 bcl-2-Associated X Protein L-Lactate Dehydrogenase CASP3 protein, human Caspase 3 Caspases
Topics	Apoptosis (genetics) Blotting, Western Caspase 3 Caspases (metabolism) Cell Count Cloning, Molecular Culture Media, Serum-Free DNA, Complementary (biosynthesis, genetics) Genes, bcl-2 (genetics) Humans L-Lactate Dehydrogenase (metabolism) Membrane Proteins (genetics) Microscopy, Fluorescence Mutation Nerve Tissue Proteins (biosynthesis, genetics) Neurons (physiology) Presenilin-2 Proto-Oncogene Proteins (biosynthesis, genetics) Proto-Oncogene Proteins c-bcl-2 Transfection Tumor Cells, Cultured bcl-2-Associated X Protein

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