Linked Life Data

11432978

Source:http://linkedlifedata.com/resource/pubmed/id/11432978

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2001-7-2
pubmed:abstractText
One of the pathophysiological features of Alzheimer's disease is astrocytosis around senile plaques. Reactive astrocytes may produce proinflammatory mediators, nitric oxide, and subsequent reactive oxygen intermediates such as peroxynitrites. In the present study, we investigated the possible role of the C-terminal fragment of amyloid precursor protein (CT-APP), which is another constituent of amyloid senile plaque and an abnormal product of APP metabolism, as an inducer of astrocytosis. We report that 100 nM recombinant C-terminal 105 amino acid fragment (CT105) of APP induced astrocytosis morphologically and immunologically. CT105 exposure resulted in activation of mitogen-activated protein kinase (MAPK) pathways as well as transcription factor NF-kappaB. Pretreatment with PD098059 and/or SB203580 decreased nitric oxide (NO) production and nuclear factor-kappa B (NF-kappaB) activation. But inhibitors of NF-kappaB activation did not affect MAPKs activation whereas they abolished NO production and attenuated astrocytosis. Furthermore, conditioned media derived from CT105-treated astrocytes enhanced neurotoxicity and pretreatment with NO and peroxynitrite scavengers attenuated its toxicity. These suggest that CT-APP may participate in Alzheimer's pathogenesis through MAPKs- and NF-kappaB-dependent astrocytosis and iNOS induction.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0022-3042
pubmed:author
pubmed:issnType
Print
pubmed:volume
78
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
109-20
pubmed:dateRevised
2011-10-27
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
C-terminal fragment of amyloid precursor protein induces astrocytosis.
pubmed:affiliation
Department of Anatomy, College of Medicine, BioGrand Inc., and MRC, Chung-Ang University, 221 Huksuk-dong, Dongjak-ku, Seoul 156-756, Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't