Expression of Fos, Jun, and Krox family proteins in Alzheimer's disease.
Apoptosis is an active process of cell death characterized by distinct morphological features and is often the end result of a genetic program of events, i.e., programmed cell death (PCD). There is growing evidence supporting a role for apoptosis and/or PCD in Alzheimer's disease (AD), based on DNA fragmentation studies and recent findings of increased levels of inducible transcription factors (ITFs) such as c-Jun in AD brains. We have characterized the expression of a large range of ITFs (c-Fos, Fos B, Fos-related antigens, c-Jun, Jun B, Jun D, Krox20, and Krox24) using multiple antisera in AD postmortem hippocampi and compared this with human control hippocampi as well as Huntington's disease hippocampi and human epilepsy biopsy tissue. We found little evidence of nuclear expression of any ITF except c-Jun in the human postmortem tissue, compared with nuclear staining in biopsy tissue. We found some evidence for increased levels of c-Jun and Krox24 protein and krox24 mRNA in the CA1 region of AD hippocampi, suggesting that PCD may be involved in the pathogenesis of AD. In general, staining characteristics of ITFs varied with different antisera directed against the same protein, indicating the need for caution when interpreting results.
MacGibbon
G A
GA
Department of Pharmacology and Clinical Pharmacology, School of Medicine, The University of Auckland, New Zealand.
Lawlor
P A
PA
Walton
M
M
Sirimanne
E
E
Faull
R L
RL
Synek
B
B
Mee
E
E
Connor
B
B
Dragunow
M
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D000918:Antibody Specificity; D017209:Apoptosis; D016477:Artifacts; D015153:Blotting, Western; D004268:DNA-Binding Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D051766:Early Growth Response Protein 1; D051767:Early Growth Response Protein 2; D005260:Female; D005786:Gene Expression Regulation; D017781:Genes, Immediate-Early; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D006816:Huntington Disease / Q000378:metabolism; D017874:Immediate-Early Proteins; D007106:Immune Sera / Q000276:immunology; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D005810:Multigene Family; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D011180:Postmortem Changes; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D014157:Transcription Factors / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics
D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; C497326:EGR2 protein, human; D051766:Early Growth Response Protein 1; D051767:Early Growth Response Protein 2; C486110:Egr1 protein, rat; C497328:Egr2 protein, rat; D017874:Immediate-Early Proteins; D007106:Immune Sera; D009419:Nerve Tissue Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D014157:Transcription Factors