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Literature summary for 3.4.21.68 extracted from

  • Adibhatla, R.M.; Hatcher, J.F.
    Tissue plasminogen activator (tPA) and matrix metalloproteinases in the pathogenesis of stroke: therapeutic strategies (2008), CNS Neurol. Disord. Drug Targets, 7, 243-253.
    View publication on PubMedView publication on EuropePMC

Application

Application Comment Organism
medicine desmoteplase has additional advantages to human tPA, it is not neurotoxic and is unaffected by beta-amyloid. Desmoteplase antagonizes the neurotoxicity induced by vascular tPA possibly by competing with tPA for the low-density lipoprotein receptorrelated protein-1 binding at the BBB and thus preventing tPA access to the brain parenchyma. A phase III clinical trial of desmoteplase is halted since it has failed to demonstrate any beneficial effects in terms of neurological improvements and survival Desmodus rotundus
medicine tPA is used as a thrombolytic agent for treatment of ischemic stroke and is the only agent that has been shown to improve stroke outcome in clinical trials. Patients receive little or no benefit if tPA therapy is initiated more than 3 h after the onset of stroke, which excludes most stroke patients from tPA treatment due to the time required for transportation to medical facilities and proper diagnosis. tPA may damage the basal lamina of the blood vessels, resulting in edema, disruption of the blood-brain barrier, or hemorrhage, thus any patients with evidence of hemorrhage or who have been taking any anti-coagulant medication such as aspirin are not candidates for tPA therapy Homo sapiens

Protein Variants

Protein Variants Comment Organism
additional information tPA knockout mice are protected against kainic acid-induced hippocampal damage and are resistant to focal cerebral ischemic injury. Exogenous tPA exacerbates ischemic injury in both wild-type and tPA-null mice Mus musculus

Inhibitors

Inhibitors Comment Organism Structure
neuroserpin endogenous inhibitor, regulating tPA activity Homo sapiens
plasminogen activator inhibitor-I rapidly inactivates the catalytic activity of tPA in the blood stream Homo sapiens

Organism

Organism UniProt Comment Textmining
Desmodus rotundus
-
-
-
Homo sapiens
-
-
-
Mus musculus
-
-
-
Rattus norvegicus
-
SHR and Wistar-Kyoto rats
-

Source Tissue

Source Tissue Comment Organism Textmining
blood longer (more than 4 h) half-life in bloodstream circulation compared to human tPA (5-10 min) Desmodus rotundus
-
blood tPA has a half-life in the bloodstream in humans of 5 to 10 min. This short half-life prevents tPA from acting on subsequent and continued vessel occlusions that occur Homo sapiens
-
central nervous system tPA is expressed widely in the central nervous system and is involved in mechanisms of synaptic regulation and synaptic plasticity, both during development and in the mature brain Homo sapiens
-
additional information less tPA in SHR rats compared to Wistar-Kyoto rats after 24 h permanent middle cerebral artery occlusion Rattus norvegicus
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
Laminin + H2O tPA amplifies excitotoxic neuronal death by degrading laminin and disruption of pro-survival cell-matrix signaling Mus musculus ?
-
?
MMP-9 + H2O tPA directly or by activation of MMP-9, can have beneficial effects on recovery after stroke by promoting neurovascular repair through vascular endothelial growth factor Homo sapiens ?
-
?
additional information tPA facilitates Ca2+ influx via NMDA receptors and dopaminergic transmission via D1 receptors and long-term potentiation in the hippocampus. tPA promotes degradation of the extracellular matrix, which is important for synaptic remodeling and formation of new axonal varicosities Homo sapiens ?
-
?
PAR-1 + H2O toxic effects of tPA in stroke can be mediated through activation of PAR-1 Mus musculus ?
-
?
plasminogen + H2O
-
Homo sapiens plasmin + ?
-
?

Synonyms

Synonyms Comment Organism
Alteplase recombinant human tPA Homo sapiens
desmoteplase
-
Desmodus rotundus
plasminogen activator
-
Desmodus rotundus
Reteplase recombinant non-glycosylated form of human tPA Homo sapiens
Tissue plasminogen activator
-
Mus musculus
Tissue plasminogen activator
-
Homo sapiens
Tissue plasminogen activator
-
Rattus norvegicus
Tissue-type plasminogen activator
-
Mus musculus
Tissue-type plasminogen activator
-
Homo sapiens
Tissue-type plasminogen activator
-
Rattus norvegicus
tPA
-
Mus musculus
tPA
-
Homo sapiens
tPA
-
Rattus norvegicus