Effect of aluminium on expression and processing of amyloid precursor protein.
The environmental agent aluminium has been extensively investigated for a potential role in the aetiology of Alzheimer's disease. Despite many investigations there is at present no definite proof for any involvement. If aluminium is involved it is possible that its action is mediated through interaction with the synthesis or processing of amyloid precursor protein (APP). The present study compared aluminium loaded IMR-32 neuroblastoma cells and rat brains with control cells and brains to determine if aluminium affected APP expression and/or processing. In the IMR-32 model system aluminium had no effect on steady-state APP mRNA levels or on the ratio of individual isoforms. It also had no quantitative or qualitative effect on APP-immunoreactive bands detected in protein extracts from conditioned medium of these cells. In total cell extracts, aluminium reduced the intensity of APP-immunoreactive bands between 120-105 kDa but had no effect on a 9 kDa band. In rat brains, aluminium had no effect on APP-immunoreactive bands from soluble or insoluble-membranous extracts. The results, in general, provide no evidence for any effect of aluminium on APP expression or processing.
Neill
D
D
MRC Neurochemical Pathology Unit, Newcastle General Hospital, Newcastle upon Tyne, United Kingdom.
Leake
A
A
Hughes
D
D
Keith
A B
AB
Taylor
G A
GA
Allsop
D
D
Rima
B K
BK
Morris
C
C
Candy
J M
JM
Edwardson
J A
JA
D000535:Aluminum / Q000009:adverse effects / Q000494:pharmacology*; D000544:Alzheimer Disease / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001059:Apoproteins / Q000494:pharmacology; D015152:Blotting, Northern; D015153:Blotting, Western; D001923:Brain Chemistry / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008970:Molecular Weight; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009447:Neuroblastoma / Q000473:pathology; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D014168:Transferrin / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D016564:Amyloid beta-Protein Precursor; D001059:Apoproteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D014168:Transferrin; C028284:apotransferrin; D000535:Aluminum