Article

Pro-apoptotic function of calsenilin/DREAM/KChIP3.

Department of Life Science, Kwangju Institute of Science and Technology, Puk-gu, Kwangju 500-712, Korea.
The FASEB Journal (impact factor: 5.71). 04/2001; 15(3):589-91. DOI:10.1096/fj.00-0541fje pp.589-91
Source: PubMed

ABSTRACT Apoptotic cell death and increased production of amyloid b peptide (Ab) are pathological features of Alzheimer's disease (AD), although the exact contribution of apoptosis to the pathogenesis of the disease remains unclear. Here we describe a novel pro-apoptotic function of calsenilin/DREAM/KChIP3. By antisense oligonucleotide-induced inhibition of calsenilin/DREAM/KChIP3 synthesis, apoptosis induced by Fas, Ca2+-ionophore, or thapsigargin is attenuated. Conversely, calsenilin/DREAM/KChIP3 expression induced the morphological and biochemical features of apoptosis, including cell shrinkage, DNA laddering, and caspase activation. Calsenilin/DREAM/KChIP3-induced apoptosis was suppressed by caspase inhibitor Z-VAD and by Bcl-XL, and was potentiated by increasing cytosolic Ca2+, expression of Swedish amyloid precursor protein mutant (APPSW) or presenilin 2 (PS2), but not by a PS2 deletion lacking its C-terminus (PS2/411stop). In addition, calsenilin/DREAM/KChIP3 expression increased Ab42 production in cells expressing APPsw, which was potentiated by PS2, but not by PS2/411stop, which suggests a role for apoptosis-associated Ab42 production of calsenilin/DREAM/KChIP3.

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Keywords

Ab42 production
 
Alzheimer's disease
 
amyloid b peptide
 
antisense oligonucleotide-induced inhibition
 
apoptosis induced
 
apoptosis-associated Ab42 production
 
Apoptotic cell death
 
biochemical features
 
calsenilin/DREAM/KChIP3 expression
 
calsenilin/DREAM/KChIP3 synthesis
 
Calsenilin/DREAM/KChIP3-induced apoptosis
 
caspase activation
 
caspase inhibitor Z-VAD
 
cell shrinkage
 
cytosolic Ca2+
 
exact contribution
 
novel pro-apoptotic function
 
presenilin 2
 
PS2 deletion
 
Swedish amyloid precursor protein mutant
 

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