Linked Life Data

15191806

Source:http://linkedlifedata.com/resource/pubmed/id/15191806

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2004-6-11
pubmed:abstractText
Protease-activated receptor-1 (PAR1) is a G-protein coupled receptor that is proteolytically activated by blood-derived serine proteases. Although PAR1 is best known for its role in coagulation and hemostasis, recent findings demonstrate that PAR1 activation has actions in the central nervous system (CNS) apart from its role in the vasculature. Rodent studies have demonstrated that PAR1 is expressed throughout the brain on neurons and astrocytes. PAR1 activation in vitro and in vivo appears to influence neurodegeneration and neuroprotection in animal models of stroke and brain injury. Because of increasing evidence that PAR1 has important and diverse roles in the CNS, we explored the protein localization and function of PAR1 in human brain. PAR1 is most intensely expressed in astrocytes of white and gray matter and moderately expressed in neurons. PAR1 and GFAP co-localization demonstrates that PAR1 is expressed on the cell body and on astrocytic endfeet that invest capillaries. PAR1 activation in the U178MG human glioblastoma cell line increased PI hydrolysis and intracellular Ca(2+), indicating that PAR1 is functional in human glial-derived tumor cells. Primary cultures of human astrocytes and human glioblastoma cells respond to PAR1 activation by increasing intracellular Ca(2+). Together, these results demonstrate that PAR1 is expressed in human brain and functional in glial tumors and cultures derived from it. Because serine proteases may enter brain tissue and activate PAR1 when the blood brain barrier (BBB) breaks down, pharmacological manipulation of PAR1 signaling may provide a potential therapeutic target for neuroprotection in human neurological disorders.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0014-4886
pubmed:author
pubmed:issnType
Print
pubmed:volume
188
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
94-103
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:15191806-Astrocytes, pubmed-meshheading:15191806-Blood-Brain Barrier, pubmed-meshheading:15191806-Brain, pubmed-meshheading:15191806-Brain Neoplasms, pubmed-meshheading:15191806-Calcium, pubmed-meshheading:15191806-Calcium Signaling, pubmed-meshheading:15191806-Capillaries, pubmed-meshheading:15191806-Glial Fibrillary Acidic Protein, pubmed-meshheading:15191806-Glioblastoma, pubmed-meshheading:15191806-Glioma, pubmed-meshheading:15191806-Humans, pubmed-meshheading:15191806-Immunohistochemistry, pubmed-meshheading:15191806-Nerve Fibers, Myelinated, pubmed-meshheading:15191806-Neurons, pubmed-meshheading:15191806-Phosphatidylinositols, pubmed-meshheading:15191806-Receptor, PAR-1, pubmed-meshheading:15191806-Serine Endopeptidases, pubmed-meshheading:15191806-Tumor Cells, Cultured
pubmed:year
2004
pubmed:articleTitle
Protease-activated receptor-1 in human brain: localization and functional expression in astrocytes.
pubmed:affiliation
Department of Pharmacology, Emory University, Atlanta, GA 30322, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't