Expression of ced-3 and ced-9 homologs in Alzheimer's disease cerebral cortex.
In order to characterize cell death mechanisms involved in Alzheimer disease (AD), we quantitated the expression of ced-3 and ced-9 homologs in AD frontal cortex. Positive (ICE, ICErel-II, ICErel-III, Ich-1L, CPP32, mch2, mch3, bcl-xS, bax and bak) and negative (bcl-2, bcl-xL, MCL1 and Ich-1S) regulators of apoptosis were successively examined using a semi-quantitative technique of reverse transcription-polymerase chain reaction (RT-PCR). Total RNA was extracted from postmortem frontal cortex of AD patients (n = 7) and controls (n = 7) matched for age and autolysis time. Baseline levels of message were detected for 3 ced-3 (CPP32, Ich-1 and ICE) and 4 ced-9 homologs (bcl-x, MCL1, bcl-2 and bax) in the frontal cortex. There was an overexpression of the ICEalpha cDNA in AD patients as compared with age-matched controls (P = 0.03). Our results indicate that several ced-3 and ced-9 homologs are expressed in the adult human brain, and suggest that neuronal cell death in AD might involve an aberrant expression of ICEalpha.
Desjardins
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Neuroscience Research Unit, Hôpital St-Luc, Montreal, Quebec, Canada.
Ledoux
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D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D001329:Autolysis; D029742:Caenorhabditis elegans Proteins; D020170:Caspase 1; D053143:Caspase 2; D053148:Caspase 3; D053178:Caspase 6; D020169:Caspases; D003546:Cysteine Endopeptidases / Q000032:analysis / Q000096:biosynthesis*; D005625:Frontal Lobe / Q000378:metabolism* / Q000473:pathology; D015801:Helminth Proteins / Q000032:analysis / Q000096:biosynthesis*; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000096:biosynthesis*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D012016:Reference Values; D014158:Transcription, Genetic; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
D051017:Apoptosis Regulatory Proteins; C494772:BAK1 protein, human; C494826:BAX protein, human; C494811:BCL2L1 protein, human; D029742:Caenorhabditis elegans Proteins; C087233:Ced-9 protein, C elegans; D015801:Helminth Proteins; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; C505407:CASP3 protein, human; C505514:CASP6 protein, human; D053143:Caspase 2; D053148:Caspase 3; D053178:Caspase 6; D020169:Caspases; D003546:Cysteine Endopeptidases; C089223:ced-3 protein, C elegans; D020170:Caspase 1