PMID- 10037734
OWN - NLM
STAT- MEDLINE
DCOM- 19990330
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 10
DP  - 1999 Mar 5
TI  - Translation of the alzheimer amyloid precursor protein mRNA is up-regulated by 
      interleukin-1 through 5'-untranslated region sequences.
PG  - 6421-31
AB  - The amyloid precursor protein (APP) has been associated with Alzheimer's disease 
      (AD) because APP is processed into the beta-peptide that accumulates in amyloid 
      plaques, and APP gene mutations can cause early onset AD. Inflammation is also 
      associated with AD as exemplified by increased expression of interleukin-1 (IL-1) 
      in microglia in affected areas of the AD brain. Here we demonstrate that 
      IL-1alpha and IL-1beta increase APP synthesis by up to 6-fold in primary human 
      astrocytes and by 15-fold in human astrocytoma cells without changing the 
      steady-state levels of APP mRNA. A 90-nucleotide sequence in the APP gene 
      5'-untranslated region (5'-UTR) conferred translational regulation by IL-1alpha 
      and IL-1beta to a chloramphenicol acetyltransferase (CAT) reporter gene. 
      Steady-state levels of transfected APP(5'-UTR)/CAT mRNAs were unchanged, whereas 
      both base-line and IL-1-dependent CAT protein synthesis were increased. This APP 
      mRNA translational enhancer maps from +55 to +144 nucleotides from the 5'-cap 
      site and is homologous to related translational control elements in the 5'-UTR of 
      the light and and heavy ferritin genes. Enhanced translation of APP mRNA provides 
      a mechanism by which IL-1 influences the pathogenesis of AD.
FAU - Rogers, J T
AU  - Rogers JT
AD  - Division of Hematology, Department of Medicine, Brigham and Women's Hospital, 
      Harvard Medical School, Boston, Massachusetts 02115, USA. 
      Rogers@calvin.bwh.harvard.edu
FAU - Leiter, L M
AU  - Leiter LM
FAU - McPhee, J
AU  - McPhee J
FAU - Cahill, C M
AU  - Cahill CM
FAU - Zhan, S S
AU  - Zhan SS
FAU - Potter, H
AU  - Potter H
FAU - Nilsson, L N
AU  - Nilsson LN
LA  - eng
GR  - 6872302/PHS HHS/United States
GR  - AD09665/AD/ADAMHA HHS/United States
GR  - AR29I32717/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Interleukin-1)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Alzheimer Disease
MH  - Amyloid beta-Protein Precursor/*biosynthesis/genetics
MH  - Astrocytes
MH  - Base Sequence
MH  - Cells, Cultured
MH  - Humans
MH  - Interleukin-1/*pharmacology
MH  - Molecular Sequence Data
MH  - Protein Biosynthesis/*drug effects
MH  - RNA, Messenger/*biosynthesis/genetics
MH  - Transfection
MH  - Up-Regulation
EDAT- 1999/02/26 00:00
MHDA- 1999/02/26 00:01
CRDT- 1999/02/26 00:00
PHST- 1999/02/26 00:00 [pubmed]
PHST- 1999/02/26 00:01 [medline]
PHST- 1999/02/26 00:00 [entrez]
AID - S0021-9258(19)87603-2 [pii]
AID - 10.1074/jbc.274.10.6421 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Mar 5;274(10):6421-31. doi: 10.1074/jbc.274.10.6421.