Linked Life Data

1333299

Source:http://linkedlifedata.com/resource/pubmed/id/1333299

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
1992-12-31
pubmed:abstractText
Receptor-mediated endocytosis of tissue-type plasminogen activator (t-PA)-plasminogen activator inhibitor type 1 (PAI-1) complexes results in their clearance by Hep G2 cells. After complexes are internalized, the t-PA component is degraded. However, neither the locus of intracellular catabolism nor the fate of PAI-1 has been elucidated. To characterize these aspects of t-PA-PAI-1 catabolism, the subcellular distribution of a prebound cohort of ligand molecules was delineated after internalization at 37 degrees C. 125I-t-PA.PAI-1 and t-PA.125I-PAI-1 were compared in separate experiments. After ligand uptake, intracellular vesicles were separated on density gradients. Internalized 125I-t-PA.PAI-1 concentrated initially in endosomes. After 20 minutes of uptake, the complex began to appear in lysosomes. Subsequently, low molecular weight labeled ligand fragments were detected in culture media. A panel of lysosomotropic agents, including primaquine, chloroquine, ammonium chloride, and a combination of leupeptin and pepstatin A, inhibited degradation. When t-PA.125I-PAI-1 rather than 125I-t-PA.PAI-1 was internalized, strikingly different results were observed. Although the kinetics of internalization and the intracellular itinerary were indistinguishable for the differently labeled complexes, the 125I-PAI-1 component of t-PA.125I-PAI-1 resisted rapid degradation. After a rapid loss of t-PA, the 125I-PAI-1 moiety persisted in lysosomes for up to 180 minutes. Thus, internalized t-PA.PAI-1 is targeted to lysosomes in which PAI-1 is relatively more stable than t-PA.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Ammonium Chloride, http://linkedlifedata.com/resource/pubmed/chemical/Chloroquine, http://linkedlifedata.com/resource/pubmed/chemical/Leupeptins, http://linkedlifedata.com/resource/pubmed/chemical/Pepstatins, http://linkedlifedata.com/resource/pubmed/chemical/Plasminogen Activator Inhibitor 1, http://linkedlifedata.com/resource/pubmed/chemical/Primaquine, http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Streptomyces pepsin inhibitor, http://linkedlifedata.com/resource/pubmed/chemical/Tissue Plasminogen Activator, http://linkedlifedata.com/resource/pubmed/chemical/beta-N-Acetylhexosaminidases, http://linkedlifedata.com/resource/pubmed/chemical/leupeptin, http://linkedlifedata.com/resource/pubmed/chemical/pepstatin
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
80
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2746-54
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1992
pubmed:articleTitle
Endocytosis and lysosomal delivery of tissue plasminogen activator-inhibitor 1 complexes in Hep G2 cells.
pubmed:affiliation
Edward Mallinckrodt Departments of Cell Biology, St Louis Children's Hospital, Washington University School of Medicine, MO.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't