PMID- 15880353
OWN - NLM
STAT- MEDLINE
DCOM- 20050817
LR  - 20181201
IS  - 0360-4012 (Print)
IS  - 0360-4012 (Linking)
VI  - 80
IP  - 5
DP  - 2005 Jun 1
TI  - Short-term interleukin-1(beta) increases the release of secreted APP(alpha) via 
      MEK1/2-dependent and JNK-dependent alpha-secretase cleavage in neuroglioma U251 
      cells.
PG  - 683-92
AB  - Several lines of neuroimmunological evidence correlate the development of the 
      inflammatory responses of the brain with the formation of amyloid plaques 
      associated with the pathogenesis of neurodegenerative disorders such as 
      Alzheimer's disease. Within this context, we tested the ability of 
      interleukin-1beta (IL-1beta) to regulate the processing of beta-amyloid precursor 
      protein (beta-APP) in neuroglioma U251 cells. Our findings have shown that 
      short-term treatment with IL-1beta (2 hr) resulted in a concentration-dependent 
      decrease in the amount of the cell-associated form of beta-APP in U251 cells as 
      compared to untreated cells, whereas a 2-hr treatment with IL-1beta led to 
      increased release of secreted APP(alpha) fragment (sAPP(alpha)) into the 
      conditioned media of the cells. The fact that sAPP(alpha) is an alpha-secretase 
      cleavage metabolite of the cell-associated form of beta-APP, and the observation 
      that IL-1beta-induced sAPP(alpha) release could be blocked by tissue inhibitors 
      of metalloproteinases-1 (alpha-secretase inhibitors), suggested that 
      alpha-secretase might be involved in IL-1beta-induced-sAPP(alpha) release. 
      Moreover, to determine whether an intracellular signaling pathway mediates the 
      IL-1beta-induced increase in sAPP(alpha) secretion, we used various specific 
      signaling inhibitors and found that sAPP(alpha) release is significantly blocked 
      by the mitogen-activated protein kinase (MEK1/2) inhibitor PD98059 and the c-Jun 
      N-terminal kinase inhibitor SP600125. These findings suggested that the mechanism 
      of IL-1beta-induced-sAPP(alpha) release is dependent on MEK1/2- and JNK-activated 
      alpha-secretase cleavage in neuroglioma U251 cells.
CI  - (c) 2005 Wiley-Liss, Inc.
FAU - Ma, Guozhao
AU  - Ma G
AD  - Department of Neurology, Ruijin Hospital, Shanghai Second Medical University, 
      Shanghai, China.
FAU - Chen, Shengdi
AU  - Chen S
FAU - Wang, Xijin
AU  - Wang X
FAU - Ba, Maowen
AU  - Ba M
FAU - Yang, Hui
AU  - Yang H
FAU - Lu, Guoqiang
AU  - Lu G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci Res
JT  - Journal of neuroscience research
JID - 7600111
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Anthracenes)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Flavonoids)
RN  - 0 (Interleukin-1)
RN  - 1TW30Y2766 (pyrazolanthrone)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 1)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 2)
RN  - EC 3.4.- (Amyloid Precursor Protein Secretases)
RN  - EC 3.4.- (Endopeptidases)
RN  - EC 3.4.23.- (Aspartic Acid Endopeptidases)
RN  - EC 3.4.23.46 (BACE1 protein, human)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
SB  - IM
MH  - Amyloid Precursor Protein Secretases
MH  - Amyloid beta-Protein Precursor/*metabolism
MH  - Anthracenes/pharmacology
MH  - Aspartic Acid Endopeptidases/*metabolism
MH  - Cell Line, Tumor
MH  - Cell Survival/drug effects
MH  - Endopeptidases
MH  - Enzyme Inhibitors/pharmacology
MH  - Flavonoids/pharmacology
MH  - Glioma
MH  - Humans
MH  - Interleukin-1/*pharmacology
MH  - JNK Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism
MH  - MAP Kinase Kinase 1/antagonists & inhibitors/*metabolism
MH  - MAP Kinase Kinase 2/antagonists & inhibitors/*metabolism
MH  - MAP Kinase Signaling System/drug effects/physiology
MH  - Phosphorylation
MH  - Protein-Tyrosine Kinases/metabolism
MH  - Solubility
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
EDAT- 2005/05/10 09:00
MHDA- 2005/08/18 09:00
CRDT- 2005/05/10 09:00
PHST- 2005/05/10 09:00 [pubmed]
PHST- 2005/08/18 09:00 [medline]
PHST- 2005/05/10 09:00 [entrez]
AID - 10.1002/jnr.20515 [doi]
PST - ppublish
SO  - J Neurosci Res. 2005 Jun 1;80(5):683-92. doi: 10.1002/jnr.20515.