Linked Life Data

19549899

Source:http://linkedlifedata.com/resource/pubmed/id/19549899

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
2009-7-7
pubmed:abstractText
Recombinant plasminogen kringle 5 (rK5) has been shown to induce apoptosis of dermal microvessel endothelial cells (MvEC) in a manner that requires glucose-regulated protein 78 (GRP78). As we are interested in antiangiogenic therapy for glioblastoma tumors, and the effectiveness of antiangiogenic therapy can be enhanced when combined with radiation, we investigated the proapoptotic effects of rK5 combined with radiation on brain MvEC. We found that rK5 treatment of brain MvEC induced apoptosis in a dose- and time-dependent manner and that prior irradiation significantly sensitized (500-fold) the cells to rK5-induced apoptosis. The rK5-induced apoptosis of both unirradiated and irradiated MvEC required expression of GRP78 and the low-density lipoprotein receptor-related protein 1 (LRP1), a scavenger receptor, based on down-regulation studies with small interfering RNA, and blocking studies with either a GRP78 antibody or a competitive inhibitor of ligand binding to LRP1. Furthermore, p38 mitogen-activated protein kinase was found to be a necessary downstream effector for rK5-induced apoptosis. These data suggest that irradiation sensitizes brain MvEC to the rK5-induced apoptosis and that this signal requires LRP1 internalization of GRP78 and the activation of p38 mitogen-activated protein kinase. Our findings suggest that prior irradiation would have a dose-sparing effect on rK5 antiangiogenic therapy for brain tumors and further suggest that the effects of rK5 would be tumor specific, as the expression of GRP78 protein is up-regulated on the brain MvEC in glioblastoma tumor biopsies compared with the normal brain.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1538-7445
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
69
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5537-45
pubmed:dateRevised
2011-4-22
pubmed:meshHeading
pubmed-meshheading:19549899-Angiogenesis Inhibitors, pubmed-meshheading:19549899-Apoptosis, pubmed-meshheading:19549899-Brain, pubmed-meshheading:19549899-Brain Neoplasms, pubmed-meshheading:19549899-Cell Membrane, pubmed-meshheading:19549899-Cerebrovascular Circulation, pubmed-meshheading:19549899-Endothelium, Vascular, pubmed-meshheading:19549899-Glioblastoma, pubmed-meshheading:19549899-Heat-Shock Proteins, pubmed-meshheading:19549899-Humans, pubmed-meshheading:19549899-Immunoblotting, pubmed-meshheading:19549899-Microcirculation, pubmed-meshheading:19549899-Neovascularization, Pathologic, pubmed-meshheading:19549899-Peptide Fragments, pubmed-meshheading:19549899-Plasminogen, pubmed-meshheading:19549899-Receptors, LDL, pubmed-meshheading:19549899-Survival Analysis, pubmed-meshheading:19549899-Tumor Suppressor Proteins
pubmed:year
2009
pubmed:articleTitle
Plasminogen kringle 5 induces apoptosis of brain microvessel endothelial cells: sensitization by radiation and requirement for GRP78 and LRP1.
pubmed:affiliation
Division of Neuropathology, Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural