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malfunction
tPA-deficient ALBPLG1 mice show no difference in survival, bacterial dissemination or the pathology of GAS infection in the absence of tPA in AlbPLG1/tPA-/- mice compared to wild-type AlbPLG1 mice
metabolism
the plasminogen-plasmin (PLG-PLA) system plays a role in thrombolysis, being capable of degrading blood clots. THe system consists of plasminogen, the inactive zymogen produced principally in the liver, its activators (tissue plasminogen activator, tPA and uroquinase plasminogen activator, uPA (EC 3.4.21.73)), their inhibitors (belonging to the serpin gene superfamily, named PAI-1, PAI-2, PAI-3 and protease nexin I), the uPA receptor and, finally, the active enzyme plasmin and its inhibitor, alpha-antiplasmin (alpha-PL). Apart from its fibrinolytic function, the PLG-PLA system is important in degrading the extracellular matrix in multiple tissues contributing to cell migration, angiogenesis, tissue repair and remodelling or tumour invasion
physiological function
plasmin(ogen) acquisition is critical for invasive disease initiation by Streptococcus pyogenes (GAS), limited role of tissue-type plasminogen activator in a mouse model of Group A streptococcal infection
physiological function
tissue plasminogen activator (tPA) of paternal origin is necessary for the success of in vitro but not of in vivo fertilisation in the mouse. The presence of exogenous plasminogen drastically reduces the fertilisation rate under in vitro conditions. When plasminogen is present in combination with inhibitors (e.g. alpha-PL or EACA), the fertilisation rate is partially restored
malfunction
-
decreased serotonin levels associated with behavioral disinhibition in tissue plasminogen activator deficient -/- mice, the tPA-/- mice demonstrate an enhanced tendency to actively explore and engage in behaviors involving more exposure in the open field, O-maze and elevated plus maze
malfunction
-
altered tPA activity levels in mouse models of Alzheimer's disease and spinocerebellar ataxia type-1, SCA1. Decreased tPA activity is detected in the cortex and subcortex of Alzheimer's disease mice, whereas increased tPA activity is found in the cerebellum of SCA1 mice
physiological function
-
serine protease, which converts plasminogen into plasmin, which in turn degrades fibrin and other extracellular matrix components, tPA plays an important role in the processes of learning and memory, demonstrated at the level of behavior and synaptic plasticity, role in neurodegeneration
physiological function
-
despite its pro-fibrinolytic activity, tPA is a serine protease known to influence a number of physiological and pathological functions in the central nervous system. Accordingly, tPA mediates some of its functions in the central nervous system through N-methyl-D-aspartate receptors, low-density lipoprotein receptor-related protein, or annexin II. tPA can mediate proteolysis and subsequent delocalization of neuronal nitric oxide synthase, nNOS, thereby reducing endogenous neuronal nitric oxide release, independent of NMDA receptors, calpains, and low-density lipoprotein receptor-related proteins. tPA promotes proteolysis of nNOS through a plasmin-dependent mechanism, which is prevented in the presence of aprotinin and alpha2-antiplasmin, two blockers of the proteolytic activity of plasmin, overview
physiological function
-
ethanol exposure during developmental synaptogenesis can lead to brain defects referred to as fetal alcohol syndrome, which can include mental health problems such as cognitive deficits and mental retardation. Tissue plasminogen activator is implicated in neurodegeneration and is a critical signaling component in FAS. In wild-type mice, ethanol elicits caspase-3 activation, significant forebrain neurodegeneration, and decreases contextual fear conditioning in adults. However, tPA-deficient mice are protected from these neurotoxicities, and this protection can be abrogated by exogenous tPA. The effects of tPA are mediated by the NR2B subunit of the NMDA receptor, but tPA catalytic activity Is not required to promote ethanol-induced neurodegenration
physiological function
-
mechanism of action of tPA on oligodendrocyte survival and on the extent of white matter lesions in stroke, overview. tPA protects oligodendrocytes from apoptosis through an unexpected cytokine-like effect by the virtue of its epidermal growth factor-like domain, and tPA protects white matter from stroke-induced lesions. Aging differentially influences gray and white matter susceptibility to stroke. tPA, via extracellular regulated kinase 1/2 and Akt intracellular pathways, regulates the balance between proand antiapoptotic factors and reduces the activity of caspase 3
physiological function
-
tissue plasminogen activator is a secreted serine protease and is also proepileptic and excitotoxic. Wild-type tPA and S481A catalytically inactive tPA mutant mediate zinc uptake via the zinc influx transporter, ZIP4, overview. ZIP4 is upregulated after excitotoxin stimulation of the mouse, male and female, hippocampus. ZIP4 physically interacts with tPA, correlating with an increased intracellular zinc influx and lysosomal sequestration. This sequestration might result in neuroprotection. tPA mutants with deletion of the second kringle domain, DELTAK2, or deletion of the growth factor domain, DELTAGF, are less effective
physiological function
-
tissue plasminogen activator, tPA, and its inhibitors contribute to neurite outgrowth in the central nervous system after treatment of stroke with multipotent mesenchymal stromal cells. Critical role of tPA in facilitating neurite outgrowth. Bone marrow stromal cells modulate endogenous tPA level and activity in the ischemic boundary zone, IBZ
physiological function
-
tissue plasminogen activator, tPA, is the primary source of plasminogen activator in the brain, and is a member of the fibrinolytic system and a serine protease that converts the zymogen plasminogen into the active protease plasmin, and thus cleaves fibrin and dissolves newly formed clots. Bone marrow stromal cells significantly improve functional recovery from stroke dependent on tPA function, overview. In tPA knockout mice, no bone marrow stromal cell effect is observed on functional recovery
physiological function
-
tissue type plasminogen activator regulates myeloid-cell dependent neoangiogenesis during tissue regeneration. Serpin-resistant form of tPA expands the myeloid cell pool and mobilizes CD45+ CD11b+ proangiogenic, myeloid cells, by activating the extracellular proteases matrix metalloproteinase-9 and plasmin, a process dependent on vascular endothelial growth factor-A and Kit ligand signaling. tPA improves the incorporation of CD11b+ cells into ischemic tissues and increases expression of neoangiogenesis-related genes, including VEGF-A, kinetics and mechanism, overview. tPA can induce cell migration by binding to CD11b and degrading fibrin. Batroxobin, a drug that reduces circulating fibrinogen, prevents the tPA-mediated WBC and CD11b+ cell increase. Inhibition of VEGF signaling suppresses tPA-induced neovascularization in a model of hind limb ischemia
physiological function
-
tPA is an initiator of intravascular fibrinolysis and is a complex mediator of brain function and dysfunction. tPA participates in various forms of chronic neurodegeneration, and plays a functional role following morphine administration, epileptic seizures, traumatic brain injury and ischaemic stroke-neurological settings
physiological function
-
tPA potentiates excitotoxicity by interacting with and cleaving the N-terminal end of the NR1 subunit of N-methyl-D-aspartate receptors, leading to an increased calcium influx, Erk1/2 activation, and neurotoxicity, mechanism, overview
additional information
tPA is active in solution
additional information
-
tPA is active in solution
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Nulkar, M.W.; Darad, R.; Subramanian, M.; Pawse, A.R.
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Mus musculus
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Mus musculus (P11214), Mus musculus
brenda
Medina, M.G.; Ledesma, M.D.; Dominguez, J.E.; Medina, M.; Zafra, D.; Alameda, F.; Dotti, C.G.; Navarro, P.
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Mus musculus (P11214), Rattus norvegicus (P19637)
brenda
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Mus musculus (P11214), Mus musculus, Rattus norvegicus (P19637)
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Mus musculus
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65
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Mus musculus
brenda
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Neurobiol. Dis.
27
164-173
2007
Homo sapiens, Mus musculus
brenda
Lian, X.; Yang, L.; Gao, Q.; Yang, T.
IL-1alpha is a potent stimulator of keratinocyte tissue plasminogen activator expression and regulated by TGF-beta1
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300
185-193
2008
Mus musculus
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
Hu, K.; Lin, L.; Tan, X.; Yang, J.; Bu, G.; Mars, W.M.; Liu, Y.
tPA protects renal interstitial fibroblasts and myofibroblasts from apoptosis
J. Am. Soc. Nephrol.
19
503-514
2008
Homo sapiens, Mus musculus
brenda
Hou, S.J.; Yen, F.C.; Tsai, S.J.
Is dysfunction of the tissue plasminogen activator (tPA)-plasmin pathway a link between major depression and cardiovascular disease?
Med. Hypotheses
72
166-168
2009
Homo sapiens, Mus musculus
brenda
Pothakos, K.; Robinson, J.K.; Gravanis, I.; Marsteller, D.A.; Dewey, S.L.; Tsirka, S.E.
Decreased serotonin levels associated with behavioral disinhibition in tissue plasminogen activator deficient (tPA-/-) mice
Brain Res.
1326
135-142
2010
Mus musculus
brenda
Kim, S.; von Recum, H.A.
Endothelial progenitor populations in differentiating embryonic stem cells. II. Drug selection and functional characterization
Tissue Eng. Part A
16
1065-1074
2010
Mus musculus
brenda
Baron, A.; Hommet, Y.; Casse, F.; Vivien, D.
Tissue-type plasminogen activator induces plasmin-dependent proteolysis of intracellular neuronal nitric oxide synthase
Biol. Cell
102
539-547
2010
Mus musculus
brenda
Ohki, M.; Ohki, Y.; Ishihara, M.; Nishida, C.; Tashiro, Y.; Akiyama, H.; Komiyama, H.; Lund, L.R.; Nitta, A.; Yamada, K.; Zhu, Z.; Ogawa, H.; Yagita, H.; Okumura, K.; Nakauchi, H.; Werb, Z.; Heissig, B.; Hattori, K.
Tissue type plasminogen activator regulates myeloid-cell dependent neoangiogenesis during tissue regeneration
Blood
115
4302-4312
2010
Mus musculus, Mus musculus C57BL/6
brenda
Correa, F.; Gauberti, M.; Parcq, J.; Macrez, R.; Hommet, Y.; Obiang, P.; Hernangomez, M.; Montagne, A.; Liot, G.; Guaza, C.; Maubert, E.; Ali, C.; Vivien, D.; Docagne, F.
Tissue plasminogen activator prevents white matter damage following stroke
J. Exp. Med.
208
1229-1242
2011
Homo sapiens, Mus musculus, Mus musculus C57/BL6
brenda
Emmetsberger, J.; Mirrione, M.M.; Zhou, C.; Fernandez-Monreal, M.; Siddiq, M.M.; Ji, K.; Tsirka, S.E.
Tissue plasminogen activator alters intracellular sequestration of zinc through interaction with the transporter ZIP4
J. Neurosci.
30
6538-6547
2010
Mus musculus, Mus musculus C57BL/6
brenda
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Lab. Invest.
91
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2011
Mus musculus, Mus musculus C57/BL6J
brenda
Xin, H.; Li, Y.; Shen, L.H.; Liu, X.; Wang, X
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PLoS ONE
5
e9027
2010
Mus musculus
brenda
Noel, M.; Norris, E.H.; Strickland, S.
Tissue plasminogen activator is required for the development of fetal alcohol syndrome in mice
Proc. Natl. Acad. Sci. USA
108
5069-5074
2011
Mus musculus
brenda
Macrez, R.; Bezin, L.; Le Mauff, B.; Ali, C.; Vivien, D.
Functional occurrence of the interaction of tissue plasminogen activator with the NR1 subunit of N-methyl-D-aspartate receptors during stroke
Stroke
41
2950-2955
2010
Mus musculus, Mus musculus Swiss
brenda
Shen, L.H.; Xin, H.; Li, Y.; Zhang, R.L.; Cui, Y.; Zhang, L.; Lu, M.; Zhang, Z.G.; Chopp, M.
Endogenous tissue plasminogen activator mediates bone marrow stromal cell-induced neurite remodeling after stroke in mice
Stroke
42
459-464
2011
Mus musculus, Mus musculus C57BL/6
brenda
Ly, D.; Donahue, D.; Walker, M.J.; Ploplis, V.A.; McArthur, J.D.; Ranson, M.; Castellino, F.J.; Sanderson-Smith, M.L.
Characterizing the role of tissue-type plasminogen activator in a mouse model of Group A streptococcal infection
Microbes Infect.
21
412-417
2019
Mus musculus (P11214), Mus musculus
brenda
Garcia-Vazquez, F.A.; Soriano-Ubeda, C.; Laguna-Barraza, R.; Izquierdo-Rico, M.J.; Navarrete, F.A.; Visconti, P.E.; Gutierrez-Adan, A.; Coy, P.
Tissue plasminogen activator (tPA) of paternal origin is necessary for the success of in vitro but not of in vivo fertilisation in the mouse
Reprod. Fertil. Dev.
31
433-442
2019
Mus musculus (P11214), Mus musculus, Mus musculus CD-1 (P11214)
brenda