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Synonyms
tpa, plasminogen activator, tissue plasminogen activator, rt-pa, tissue-type plasminogen activator, alteplase, recombinant tissue plasminogen activator, reteplase, r-tpa, tissue-plasminogen activator,
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2,7-bis-(4-amidinobenzylidene)-cycloheptanone-(1)dihydrochloride
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H89
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inhibits dibutyryl-cAMP-mediated changes in tPA activity without affecting metalloproteinase-9 activity
lipopolysaccharide
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decreases tPA activity. Co-treatment with dibutyryl-cAMP and lipopolysaccharide dose-dependently prevents lipopolysaccharide-induced downregulation of tPA activity
plasminogen activator inhibitor type-1
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major inhibitor of tissue-type plasminogen activator in the blood
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plasminogen activator inhibitor-1
Rp-cAMP
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inhibits dibutyryl-cAMP-mediated changes in tPA activity without affecting metalloproteinase-9 activity
xenon
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intraischemic xenon dose-dependently inhibits tissue-type plasminogen activator-induced thrombolysis and subsequent reduction of ischemic brain damage, postischemic xenon virtually suppresses ischemic brain damage and tissue-type plasminogen activator-induced brain hemorrhages and disruption of the blood-brain barrier, therefore xenon should not be administered before or together with a tissue-type plasminogen activator therapy
plasminogen activator inhibitor-1
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plays a major role in the regulation of tPA activity
plasminogen activator inhibitor-1
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PAI-1, astrocyte-derived, induction of PAI-1 by lipopolysaccharide stimulation in astrocytes
plasminogen activator inhibitor-1
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PAI-1, endogenous inhibitor of tPA in the cell
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metabolism
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tissue-type plasminogen activator functions as the main activator of the fibrinolytic process in the intravascular compartment
additional information
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alteplase is the full-length recombinant human TPA, while reteplase, K2P, is the domain deletion mutant comprising only the Kringle-2 domain and protease domain of TPA. Reteplase shows a better protective effect than alteplase, suggesting that F, P, or K1 domain in TPA diminishes the brain-protective effect
physiological function
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serine protease
physiological function
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tissue-type plasminogen activator is a serine protease that converts plasminogen into the active enzyme plasmin, which in turn degrades the fibrin of the forming thrombus
physiological function
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regulatory mechanism of the plasminogen activator system in astrocytes, overview
physiological function
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the Kringle-2 domain, residues 176-262 of TPA, is the essential structure required for the brain-protective activity of TPA, employing the rat middle cerebral artery occlusion, MCAO, model. The Kringle-2 domain of tissue plasminogen activator significantly reduces mortality and brain infarction in middle cerebral artery occlusion rats. Tissue plasminogen activator shows brainprotective activity within the first 15 min after cerebral ischemia in rats
physiological function
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tPA is a pivotal player in slowly progressing activity deprivation-induced neurodegeneration, e.g. induced by blockade of neuronal activity using tetrodotoxin, TTX. Neurons degenerate slowly and die in a manner resembling neurodegenerative diseases-induced neuronal cell death. Transfection of an endogenous tPA inhibitor, plasminogen activator inhibitor-1, protected the TTX-exposed neurons from dying
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Lijnen, H.R.; Webb, P.D.; van Hoef, B.; De Cock, F.; Stassen, J.M.; Prior, S.D.; Collen, D.
Biochemical and biological properties of a recombinant tissue-type plasminogen activator derived from the rat JMI-229 cell line
Thromb. Haemost.
67
239-247
1992
Rattus norvegicus
brenda
Medina, M.G.; Ledesma, M.D.; Dominguez, J.E.; Medina, M.; Zafra, D.; Alameda, F.; Dotti, C.G.; Navarro, P.
Tissue plasminogen activator mediates amyloid-induced neurotoxicity via Erk1/2 activation
EMBO J.
24
1706-1716
2005
Mus musculus (P11214), Rattus norvegicus (P19637)
brenda
Hu, K.; Yang, J.; Tanaka, S.; Gonias, S.L.; Mars, W.M.; Liu, Y.
Tissue-type plasminogen activator acts as a cytokine that triggers intracellular signal transduction and induces matrix metalloproteinase-9 gene expression
J. Biol. Chem.
281
2120-2127
2006
Mus musculus (P11214), Mus musculus, Rattus norvegicus (P19637)
brenda
Komoriya, K.; Kato, Y.; Hayashi, Y.; Ohsuye, K.; Nishigaki, R.; Sugiyama, Y.
Characterization of the hepatic disposition of lanoteplase, a rationally designed variant of tissue plasminogen activator in rodents
Drug Metab. Dispos.
35
469-475
2007
Rattus norvegicus
brenda
Adibhatla, R.M.; Hatcher, J.F.
Tissue plasminogen activator (tPA) and matrix metalloproteinases in the pathogenesis of stroke: therapeutic strategies
CNS Neurol. Disord. Drug Targets
7
243-253
2008
Homo sapiens, Mus musculus, Rattus norvegicus, Desmodus rotundus
brenda
Lee, S.Y.; Kim, H.J.; Lee, W.J.; Joo, S.H.; Jeon, S.J.; Kim, J.W.; Kim, H.S.; Han, S.H.; Lee, J.; Park, S.H.; Cheong, J.H.; Kim, W.K.; Ko, K.H.; Shin, C.Y.
Differential regulation of matrix metalloproteinase-9 and tissue plasminogen activator activity by the cyclic-AMP system in lipopolysaccharide-stimulated rat primary astrocytes
Neurochem. Res.
33
2324-2334
2008
Rattus norvegicus
brenda
David, H.N.; Haelewyn, B.; Risso, J.J.; Colloch, N.; Abraini, J.H.
Xenon is an inhibitor of tissue-plasminogen activator: adverse and beneficial effects in a rat model of thromboembolic stroke
J. Cereb. Blood Flow Metab.
30
718-728
2010
Rattus norvegicus, Homo sapiens (P00750), Homo sapiens
brenda
Hultman, K.; Bjoerklund, U.; Hansson, E.; Jern, C.
Potentiating effect of endothelial cells on astrocytic plasminogen activator inhibitor type-1 gene expression in an in vitro model of the blood-brain barrier
Neuroscience
166
408-415
2010
Rattus norvegicus
brenda
Zhang, H.; Bi, F.; Xiao, C.; Liu, J.; Wang, Z.; Liu, J.N.; Zhang, J.
The Kringle-2 domain of tissue plasminogen activator significantly reduces mortality and brain infarction in middle cerebral artery occlusion rats
Int. J. Mol. Med.
26
225-230
2010
Rattus norvegicus, Rattus norvegicus Sprague-Dawley
brenda
Kim, J.W.; Lee, S.H.; Ko, H.M.; Kwon, K.J.; Cho, K.S.; Choi, C.S.; Park, J.H.; Kim, H.Y.; Lee, J.; Han, S.H.; Ignarro, L.J.; Cheong, J.H.; Kim, W.K.; Shin, C.Y.
Biphasic regulation of tissue plasminogen activator activity in ischemic rat brain and in cultured neural cells: Essential role of astrocyte-derived plasminogen activator inhibitor-1
Neurochem. Int.
58
423-433
2011
Rattus norvegicus, Rattus norvegicus Sprague-Dawley
brenda
Schonfeld-Dado, E.; Segal, M.
Activity deprivation induces neuronal cell death: mediation by tissue-type plasminogen activator
PLoS ONE
6
e25919
2011
Rattus norvegicus
brenda