Linked Life Data

11925448

Source:http://linkedlifedata.com/resource/pubmed/id/11925448

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
24
pubmed:dateCreated
2002-6-10
pubmed:abstractText
Mutations in the Notch3 receptor result in the cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephelopathy (CADASIL) syndrome, a heritable arteriopathy predisposing to early onset stroke. Based upon clinical evidence that CADASIL arteriopathy results in degeneration and loss of vascular smooth muscle cells (VSMC) from the arterial wall, we postulated that Notch3 signaling is a critical determinant of VSMC survival. We initially established that both transient and constitutive Notch3 signaling promoted VSMC survival in response to the proapoptotic Fas ligand (FasL). Resistance to FasL-induced apoptosis was associated with the induction of c-FLIP, a primary inhibitor of the FasL signaling pathway. We determined that Notch3's regulation of c-FLIP was independent of the activity of the classical DNA-binding protein, RBP-Jk, but dependent upon cross-talk activation of the ERK/MAPK pathway. We extended our observations to the in vivo context by determining a coordinate regulation of Notch3 and c-FLIP within the arterial wall in response to injury. Furthermore, we defined that expression levels of Notch3 and c-FLIP are coordinately up-regulated within the neointima of remodeled arteries. Taken together, these findings provide initial evidence that Notch3 signaling may be a critical determinant of VSMC survival and vascular structure by modulating the expression of downstream mediators of apoptosis via signaling cross-talk with the ERK/MAPK pathway.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
14
pubmed:volume
277
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
21723-9
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:11925448-Animals, pubmed-meshheading:11925448-Aorta, pubmed-meshheading:11925448-Apoptosis, pubmed-meshheading:11925448-CASP8 and FADD-Like Apoptosis Regulating Protein, pubmed-meshheading:11925448-Carotid Arteries, pubmed-meshheading:11925448-Carrier Proteins, pubmed-meshheading:11925448-Cell Survival, pubmed-meshheading:11925448-Cells, Cultured, pubmed-meshheading:11925448-Down-Regulation, pubmed-meshheading:11925448-Enzyme Activation, pubmed-meshheading:11925448-Fas Ligand Protein, pubmed-meshheading:11925448-Intracellular Signaling Peptides and Proteins, pubmed-meshheading:11925448-MAP Kinase Signaling System, pubmed-meshheading:11925448-Male, pubmed-meshheading:11925448-Membrane Glycoproteins, pubmed-meshheading:11925448-Mitogen-Activated Protein Kinases, pubmed-meshheading:11925448-Muscle, Smooth, pubmed-meshheading:11925448-Plasmids, pubmed-meshheading:11925448-Protein Binding, pubmed-meshheading:11925448-Proto-Oncogene Proteins, pubmed-meshheading:11925448-RNA, Messenger, pubmed-meshheading:11925448-Rats, pubmed-meshheading:11925448-Rats, Sprague-Dawley, pubmed-meshheading:11925448-Receptors, Cell Surface, pubmed-meshheading:11925448-Retroviridae, pubmed-meshheading:11925448-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:11925448-Signal Transduction, pubmed-meshheading:11925448-Time Factors, pubmed-meshheading:11925448-Transcription, Genetic, pubmed-meshheading:11925448-Transfection, pubmed-meshheading:11925448-Up-Regulation
pubmed:year
2002
pubmed:articleTitle
Notch3 signaling in vascular smooth muscle cells induces c-FLIP expression via ERK/MAPK activation. Resistance to Fas ligand-induced apoptosis.
pubmed:affiliation
Cardiovascular Research Institute, Morehouse School of Medicine, Atlanta, Georgia 30310, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.