Impacts of tissue-type plasminogen activator(tPA) on neuronal survival

Frontiers in Cellular Neuroscience

Volumn 9, Issue OCTOBER, 2015, Pages

  Chevilley, Arnaud ^a   Lesept, Flavie ^a   Lenoir, Sophie ^a   Ali, Carine ^a   Parcq, Jérôme ^a   Vivien, Denis ^a  

^a UNIVERSITÉ DE CAEN   (France)

Author keywords

Apoptosis; Differential effects; Excitotoxicity; NMDA receptors; Tissue type plasminogen activator

Indexed keywords

NEUROSERPIN; PLASMINOGEN ACTIVATOR INHIBITOR 1; POSTSYNAPTIC DENSITY PROTEIN 95; TISSUE PLASMINOGEN ACTIVATOR;

APOPTOSIS; BRAIN INJURY; CELL SURVIVAL; EXCITOTOXICITY; HIPPOCAMPUS; NERVE CELL; NERVE CELL NECROSIS; NEUROPROTECTION; NEUROTOXICITY; NEUROTRANSMISSION; NONHUMAN; PROTEIN DEGRADATION; PROTEIN EXPRESSION; REVIEW; TISSUE SURVIVAL;

EID: 84947584380     PISSN: 16625102     EISSN: None     Source Type: Journal    
DOI: 10.3389/fncel.2015.00415     Document Type: Review

References (126)

1. Astrup, T., and Permin, P. M. (1947). Fibrinolysis in the animal organism. Nature 159:681. doi: 10.1038/159681b0
2. Astrup, T., and Stage, A. (1952). Isolation of a soluble fibrinolytic activator from animal tissue. Nature 170:929. doi: 10.1038/170 929a0
3. Badiola, N., Penas, C., Miñano-Molina, A., Barneda-Zahonero, B., Fadó, R., Sánchez-Opazo, et al. (2011). Induction of ER stress in response to oxygen- glucose deprivation of cortical cultures involves the activation of the PERK and IRE-1 pathways and of caspase-12. Cell Death Dis. 2:e149. doi: 10.1038/cddis.2011.31
4. Barker-Carlson, K., Lawrence, D. A., and Schwartz, B. S. (2002). Acyl- enzyme complexes between tissue-type plasminogen activator and neuroserpin are short-lived in Vitro. J. Biol. Chem. 277, 46852-46857. doi: 10.1074/jbc.M207740200
5. Baron, A., Montagne, A., Cassé, F., Launay, S., Maubert, E., Ali, C., et al. . NR2D-containing NMDA receptors mediate tissue plasminogen activator-promoted neuronal excitotoxicity. Cell Death Differ. 17, 860-871. doi: 10.1038/cdd.2009.172
6. Benchenane, K., Berezowski, V., Ali, C., Fernández-Monreal, M., López- Atalaya, J. P., Brillault, J., et al. (2005). Tissue-type plasminogen activator crosses the intact blood-brain barrier by low-density lipoprotein receptor- related protein-mediated transcytosis. Circulation 111, 2241-2249. doi: 10.1161/01.CIR.0000163542.48611.A2
7. Benchenane, K., Castel, H., Boulouard, M., Bluthe, R., Fernández-Monreal,M., Roussel, B. D., et al. (2007). Anti-NR1 N-terminal-domain vaccination unmasks the crucial action of tPA on NMDA-receptor-mediated toxicity and spatial memory. J. Cell Sci. 120, 578-585. doi: 10.1242/jcs.03354
8. Berg, D. T., Burck, P. J., Berg, D. H., and Grinnell, B. W. (1993). Kringle glycosylation in a modified human tissue plasminogen activator improves functional properties. Blood 81, 1312-1322.
9. Berg, D. T., and Grinnell, B. W. (1991). Signal and propeptide processing of human tissue plasminogen activator: activity of a pro-tPA derivative. Biochem. Biophys. Res. Commun. 179, 1289-1296. doi: 10.1016/0006-291X(91)91713-M
10. Bertrand, T., Lesept L., Chevilley, A., Lenoir, S., Aimable, M., Briens, A., et al. (2015). Conformations of tissue plasminogen activator (tPA) orchestrate neuronal survival by a crosstalk between EGFR and NMDAR. Cell Death Dis. (in press).
11. Binder, B. R., Spragg, J., and Austen, K. F. (1979). Purification and characterization of human vascular plasminogen activator derived from blood vessel perfusates. J. Biol. Chem. 254, 1998-2003.
12. Boose, J. A., Kuismanen, E., Gerard, R., Sambrook, J., and Gething, M. J. (1989). The single-chain form of tissue-type plasminogen activator has catalytic activity: studies with a mutant enzyme that lacks the cleavage site. Biochemistry 28, 635-643. doi: 10.1021/bi00428a033
13. Borisov, O. V., Field, M., Ling, V. T., and Harris, R. J. (2009). Characterization of oligosaccharides in recombinant tissue plasminogen activator produced in Chinese hamster ovary cells: two decades of analytical technology development. Anal. Chem. 81, 9744-9754. doi: 10.1021/ac901498k
14. Buisson, A., Nicole, O., Docagne, F., Sartelet, H., Mackenzie, E. T., and Vivien, D. (1998). Up-regulation of a serine protease inhibitor in astrocytes mediates the neuroprotective activity of transforming growth factor beta1. FASEB J. 12, 1683-1691.
15. Campbell, B. C. V., Mitchell, P. J., Kleinig, T. J., Dewey, H. M., Churilov, L., Yassi, N., et al. (2015). Endovascular therapy for ischemic stroke with perfusion-imaging selection. N. Engl. J. Med. 372, 1009-1018. doi: 10.1056/NEJMoa1414792
16. Cassé, F., Bardou, I., Danglot, L., Briens, A., Montagne, A., Parcq, J., et al. (2012). Glutamate controls tPA recycling by astrocytes, which in turn influences glutamatergic signals. J. Neurosci. 32, 5186-5199. doi: 10.1523/JNEUROSCI.5296-11.2012
17. Centonze, D., Saulle, E., Pisani, A., Bonsi, P., Tropepi, D., Bernardi, G., et al. (2002). Tissue plasminogen activator is required for striatal post-ischemic synaptic potentiation. Neuroreport 13, 115-118. doi: 10.1097/00001756-20020121000027
18. Christensen, L. R., and Macleod, C. M. (1945). A proteolytic enzyme of serum: characterization, activation, and reaction with inhibitors. J. Gen. Physiol. 28, 559-583. doi: 10.1085/jgp.28.6.559
19. Collen, D., and Lijnen, H. R. (1991). Basic and clinical aspects of fibrinolysis and thrombolysis. Blood 78, 3114-3124.
20. Collen, D., and Lijnen, H. R. (2009). The tissue-type plasminogen activator story. Arterioscler. Thromb. Vasc. Biol. 29, 1151-1155. doi: 10.1161/ATVBAHA.108.179655
21. Collen, D., Rijken, D. C., Van Damme, J., and Billiau, A. (1982). Purification of human tissue-type plasminogen activator in centigram quantities from human melanoma cell culture fluid and its conditioning for use in vivo. Thromb. Haemost. 48, 294-296.
22. Conradi, H. (1902). Uber die Beziehung der Autolyse zur Blutgerinnung. Beitr. chem. Physiol. Path. 1:136.
23. Cops, E. J., Sashindranath, M., Daglas, M., Short, K. M., da Fonseca Pereira, C., Pang, T. Y., et al. (2013). Tissue-type plasminogen activator is an extracellular mediator of Purkinje cell damage and altered gait. Exp. Neurol. 249, 8-19. doi: 10.1016/j.expneurol.2013.08.001
24. Correa, F., Gauberti, M., Parcq, J., Macrez, R., Hommet, Y., Obiang, P., et al. (2011). Tissue plasminogen activator prevents white matter damage following stroke. J. Exp. Med. 208, 1229-1242. doi: 10.1084/jem.20101880
25. Denis, P. S. (1838). Essai sur l'Application de la Chimie a l’Etude Physiologique Du sangde lHomme. Paris: JB Balliéere.
26. Denys, J., and de Marbaix, H. (1889). Les peptonisations provoquees par le chloroforme. Cellule 5, 197-251.
27. Echeverry, R., Wu, J., Haile, W. B., Guzman, J., and Yepes, M. (2010). Tissue-type plasminogen activator is a neuroprotectant in the mouse hippocampus. J. Clin. Invest. 120, 2194-2205. doi: 10.1172/JCI41722.2194
28. Einarsson, M., Brandt, J., and Kaplan, L. (1985). Large-scale purification ofhuman tissue-type plasminogen activator using monoclonal antibodies. Biochim. Biophys. Acta 830, 1-10. doi: 10.1016/0167-4838(85)90123-2
29. Fernández-Monreal, M., López-Atalaya, J. P., Benchenane, K., Cacquaevel, M., Dulin, F., Le Caer, J. P., et al. (2004). Arginine 260 of the amino- terminal domain of NR1 subunit is critical for tissue-type plasminogen activator-mediated enhancement of N-methyl-D-aspartate receptor signaling. J. Biol. Chem. 279, 50850-50856. doi: 10.1074/jbc.M407069200
30. Flavin, M. P., and Zhao, G. (2001). Hippocampal neurons from oxygen- glucose deprivation injury. J. Neurosci. Res. 63, 388-394. doi: 10.1002/1097-4547(20010301)63:5
31. Fleisher, M. S., and Loeb, L. (1915). Further investigations on the mode of action of substances inhibiting tumor grozcth and on immunisation against these substances. J. Exp. Med. 21, 155-163. doi: 10.1084/jem.21.2.155
32. Fredriksson, L., Li, H., Fieber, C., Li, X., and Eriksson, U. (2004). Tissue plasminogen activator is a potent activator of PDGF-CC. EMBO J. 23, 3793-3802. doi: 10.1038/sj.emboj.7600397
33. Gabriel, C., Ali, C., Lesne, S., Fernández-Monreal, M., Docagne, F., Plawinski, L., et al. (2003). Transforming growth factor alpha-induced expression of type 1 plasminogen activator inhibitor in astrocytes rescues neurons from excitotoxicity. FASEB J. 17, 277-279. doi: 10.1096/fj.02-0403fje
34. Goyal, M., Demchuk, A. M., Menon, B. K., Eesa, M., Rempel, J. L., Thornton, J., et al. (2015). Randomized assessment of rapid endovascular treatment of ischemic stroke. N. Engl. J. Med. 372, 1019-1030. doi: 10.1056/NEJMoa1414905
35. Guo, H., Barrett, T. M., Zhong, Z., Fernandez, J. A., Griffin, J. H., Freeman, R. S., et al. (2011). Protein S blocks the extrinsic apoptotic cascade in tissue plasminogen activator/N-methyl D-aspartate-treated neurons via Tyro3-Akt- FKHRL1 signaling pathway. Mol. Neurodegener. 6:13. doi: 10.1186/1750-13266-13
36. Haile, W. B., Wu, J., Echeverry, R., Wu, F., An, J., and Yepes, M. (2012). Tissue- type plasminogen activator has a neuroprotective effect in the ischemic brain mediated by neuronal TNF-a. J. Cereb. Blood Flow Metab. 32, 57-69. doi: 10.1038/jcbfm.2011.106
37. Hajjar, K. A., and Reynolds, C. M. (1994). alpha-Fucose-mediated binding and degradation of tissue-type plasminogen activator byHepG2 cells. J. Clin. Invest. 93, 703-710. doi: 10.1172/JCI117023
38. Harris, R. J., Leonard, C. K., Guzzetta, A. W., and Spellman, M. W. (1991). Tissue plasminogen activator has an O-linked fucose attached to threonine- 61 in the epidermal growth factor domain. Biochemistry 30, 2311-2314. doi: 10.1021/bi00223a004
39. Head, B. P., Patel, H. H., Niesman, I. R., Drummond, J. C., Roth, D. M., and Patel, P. M. (2009). Inhibition of p75 neurotrophin receptor attenuates isoflurane-mediated neuronal apoptosis in the neonatal central nervous system. Anesthesiology 110, 813-825. doi: 10.1097/ALN.0b013e31819b602b
40. Hedin, S. G. (1903). On the presence of a proteolytic enzyme in the normal serum ofthe ox. J. Physiol. 30, 195-201. doi: 10.1113/jphysiol.1903.sp000989
41. Henry, V. J., Lecointre, M., Laudenbach, V., Ali, C., Macrez, R., Jullienne, A., et al. (2013). High t-PA release by neonate brain microvascular endothelial cells under glutamate exposure affects neuronal fate. Neurobiol. Dis. 50, 201-208. doi: 10.1016/j.nbd.2012.10.020
42. Hetman, M., Cavanaugh, J. E., Kimelman, D., and Xia, Z. (2000). Role of glycogen synthase kinase-3beta in neuronal apoptosis induced by trophic withdrawal. J. Neurosci. 20, 2567-2574.
43. Ichinose, A., Kisiel, W., and Fujikawa, K. (1984). Proteolytic activation of tissue plasminogen activator by plasma and tissue enzymes. FEBS Lett. 175, 412-418. doi: 10.1016/0014-5793(84)80779-6
44. Jaques, A. J., Opdenakker, G., Rademacher, T. W., Dwek, R. A., and Zamze, S. E. (1996). The glycosylation of Bowes melanoma tissue plasminogen activator: lectin mapping, reaction with anti-L2/HNK-1 antibodies and the presence of sulphated/glucuronic acid containing glycans. Biochem. J. 316, 427-437. doi: 10.1042/bj3160427
45. Jörnvall, H., Pohl, G., Bergsdorf, N., and Wallén, P. (1983). Differential proteolysis and evidence for a residue exchange in tissue plasminogen activator suggest possible association between two types of protein microheterogeneity. FEBS Lett. 156, 47-50. doi: 10.1016/0014-5793(83)80245-2
46. Jullienne, A., Montagne, A., Orset, C., Lesept F., Jane, D. E., Monaghan, D. T., et al. (2011). Selective inhibition of GluN2D-containing N-methyl-D-aspartate receptors prevents tissue plasminogen activator-promoted neurotoxicity both in vitro and in vivo. Mol. Neurodegener. 6:68. doi: 10.1186/17501326-6-68
47. Kim, H. K., Lee, S. Y., Oh, H. K., Kang, B. H., Ku, H. J., Lee, Y., et al. (2003). Inhibition of endothelial cell proliferation by the recombinant kringle domain of tissue-type plasminogen activator. Biochem. Biophys. Res. Commun. 304, 740-746. doi: 10.1016/S0006-291X(03)00656-9
48. Kim, Y., Park, J. H., Hong, S. H., and Koh, J. Y. (1999). Nonproteolytic neuroprotection by human recombinant tissue plasminogen activator. Science 284, 647-650. doi: 10.1126/science.284.5414.647
49. Kuiper, J., Van't Hof, A., Otter, M., Biessen, E. A., Rijken, D. C., and van Berkel, T. J. (1996). Interaction of mutants of tissue-type plasminogen activator with liver cells: effect of domain deletions. Biochem. J. 313, 775-780. doi: 10.1042/bj3130775
50. Kvajo, M., Albrecht, H., Meins, M., Hengst, U., Troncoso, E., Lefort, S., et al. (2004). Regulation of brain proteolytic activity is necessary for the in vivo function of NMDA receptors. J. Neurosci. 24, 9734-9743. doi: 10.1523/JNEUROSCI.3306-04.2004
51. Lamba, D., Bauer, M., Huber, R., Fischer, S., Rudolph, R., Kohnert, U., et al. (1996). The 2.3 A crystal structure of the catalytic domain of recombinant two- chain human tissue-type plasminogen activator. J. Mol. Biol. 258, 117-135. doi: 10.1006/jmbi.1996.0238
52. Larsen, G. R., Henson, K., and Blue, Y. (1988). Variants of human tissue-type plasminogen activator.. J. Biol. Chem. 263, 1023-1029.
53. Launay, S., Maubert, E., Lebeurrier, N., Tennstaedt, A., Campioni, M., Docagne, F., et al. (2008). HtrA1-dependent proteolysis ofTGF-beta controls both neuronal maturation and developmental survival. Cell Death Differ. 15, 1408-1416. doi: 10.1038/cdd.2008.82
54. Lebeurrier, N., Liot, G., López-Atalaya, J. P., Orset, C., Fernández-Monreal, M., Sonderegger, P., et al. (2005). The brain-specific tissue-type plasminogen activator inhibitor, neuroserpin, protects neurons against excitotoxicity both in vitro and in vivo. Mol. Cell. Neurosci. 30, 552-558. doi: 10.1016/j.mcn.2005.09.005
55. Lee, H. Y., Hwang, I. Y., Im, H., Koh, J. Y., and Kim, Y. H. (2007). Non-proteolytic neurotrophic effects of tissue plasminogen activator on cultured mouse cerebrocortical neurons. J. Neurochem. 101, 1236-1247. doi: 10.1111/j.1471-4159.2007.04417.x
56. Lemarchand, E., Maubert, E., Haelewyn, B., Ali, C., Rubio, M., and Vivien, D. (2015). Stressed neurons protect themselves by a tissue-type plasminogen activator-mediated EGFR-dependent mechanism. Cell Death Differ. doi: 10.1038/cdd.2015.76 [Epub ahead of print].
57. Li, J., Ma, Y., Teng, Y. D., Zheng, K., Vartanian, T. K., Snyder, E. Y., et al. (2006). Purkinje neuron degeneration in nervous (nr) mutant mice is mediated by a metabolic pathway involving excess tissue plasminogen activator. Proc. Natl. Acad. Sci. U.S.A. 103, 7847-7852. doi: 10.1073/pnas.0602440103
58. Li, J., Yu, L., Gu, X., Ma, Y., Pasqualini, R., Arap, W., et al. (2013). Tissue plasminogen activator regulates Purkinje neuron development and survival. Proc. Natl. Acad. Sci. U.S.A. 110, E2410-E2419. doi: 10.1073/pnas.1305010110
59. Liberatore, G. T., Samson, A., Bladin, C., Schleuning, W. D., and Medcalf, R. L. (2003). Vampire bat salivary plasminogen activator (desmoteplase): a unique fibrinolytic enzyme that does not promote neurodegeneration. Stroke 34, 537-543. doi: 10.1161/01.STR.0000049764.49162.76
60. Liot, G., Benchenane, K., Lévéille, F., López-Atalaya, J. P., Fernández-Monreal, M., Ruocco, A., et al. (2004). 2,7-Bis-(4-amidinobenzylidene)-cycloheptan- 1-one dihydrochloride, tPA stop, prevents tPA-enhanced excitotoxicity both in vitro and in vivo. J. Cereb. Blood Flow Metab. 24, 1153-1159. doi: 10.1097/01.WCB.0000134476.93809.75
61. Liot, G., Roussel, B. D., Lebeurrier, N., Benchenane, K., López-Atalaya, J. P., Vivien, D., et al. (2006). Tissue-type plasminogen activator rescues neurones from serum deprivation-induced apoptosis through a mechanism independent of its proteolytic activity. J. Neurochem. 98, 1458-1464. doi: 10.1111/j.1471-4159.2006.03982.x
62. Liu, D., Cheng, T., Guo, H., Fernandez, J. A., Griffin, J. H., Song, X., et al. (2004). Tissue plasminogen activator neurovascular toxicity is controlled by activated protein C. Nat. Med. 10, 1379-1383. doi: 10.1038/nm1122
63. López-Atalaya, J. P., Roussel, B. D., Ali, C., Maubert, E., Petersen, K. U., Berezowski, V., et al. (2007). Recombinant Desmodus rotundus salivary plasminogen activator crosses the blood-brain barrier through a low- density lipoprotein receptor-related protein-dependent mechanism without exerting neurotoxic effects. Stroke 38, 1036-1043. doi: 10.1161/01.STR.0000258100.04923.84
64. López-Atalaya, J. P., Roussel, B. D., Levrat, D., Parcq, J., Nicole, O., Hommet, Y., et al. (2008). Toward safer thrombolytic agents in stroke: molecular requirements for NMDA receptor-mediated neurotoxicity. J. Cereb. Blood Flow Metab. 28, 1212-1221. doi: 10.1038/jcbfm.2008.14
65. Lu, W., and Tsirka, S. E. (2002). Partial rescue of neural apoptosis in the Lurcher mutant mouse through elimination of tissue plasminogen activator. Development 129, 2043-2050.
66. Ma, J., Yu, D., Tong, Y., and Mao, M. (2012). Effect of neuroserpin in a neonatal hypoxic-ischemic injury model ex vivo. Biol. Res. 45, 357-362. doi: 10.4067/S0716-97602012000400005
67. Macfarlane, R. G., and Biggs, R. (1948). Fibrinolysis; its mechanism and significance. Blood 3, 1167-1187.
68. Macrez, R., Bezin, L., Le Mauff, B., Ali, C., and Vivien, D. (2010). 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. doi: 10.1161/STROKEAHA.110.592360
69. Madison, E. L., Kobe, A., Gething, M. J., Sambrook, J. F., and Goldsmith, E. J. (1993). Converting tissue plasminogen activator to a zymogen: a regulatory triad of Asp-His-Ser. Science 262, 419-421. doi: 10.1126/science.8211162
70. Mantuano, E., Lam, M. S., and Gonias, S. L. (2013). LRP1 assembles unique co-receptor systems to initiate cell-signaling in response to tissue-type plasminogen activator and myelin-associated glycoprotein. J. Biol. Chem. 288, 34009-34018. doi: 10.1074/jbc.M113.509133
71. Mantuano, E., Lam, M. S., Shibayama, M., Campana, W. M., and Gonias, S. L. (2015). The NMDA receptor functions independently and as an LRP1 coreceptor to promote Schwann cell survival and migration. J. Cell Sci. 128, 3478-3488. doi: 10.1242/jcs.173765
72. Martin, A. M., Kuhlmann, C., Trossbach, S., Jaeger, S., Waldron, E., Roebroek, A., et al. (2008). The functional role of the second NPXY motif of the LRP1 p-chain in tissue-type plasminogen activator-mediated activation of N-methyl-D-aspartate receptors. J. Biol. Chem. 283, 12004-12013. doi: 10.1074/jbc.M707607200
73. Mattson, M.P., andDuan, W. (1999). “Apoptotic” biochemical cascades in synaptic compartments: roles in adaptive plasticity and neurodegenerative disorders. J. Neurosci. Res. 58, 152-166. doi: 10.1002/(SICI)1097-4547(19991001)58
74. Matys, T., and Strickland, S. (2003). Tissue plasminogen activator and NMDA receptor cleavage. Nat. Med. 9, 371-372. doi: 10.1038/nm0403-371
75. Medina, M. G., Ledesma, M. D., Domínguez, J. E., Medina, M., Zafra, D., Alameda, F., et al. (2005). Tissue plasminogen activator mediates amyloid- induced neurotoxicity via Erk1/2 activation. EMBO J. 24, 1706-1716. doi: 10.1038/sj.emboj.7600650
76. Montagne, A., Hébert, M., Jullienne, A., Lesept F., Le Béhot, A., Louessard, M., et al. (2012). Memantine improves safety of thrombolysis for stroke. Stroke 43, 2774-2781. doi: 10.1161/STROKEAHA.112.669374
77. Morgagni, J. B. (1761). De Sedibus, et Causis Morborum per Anatomen Indagatis. Venezia: Remondini.
78. Mori, K., Dwek, R. A., Downing, K. A., Opdenakker, G., Pauline, M., and Rudd, P. M. (1995). The activation of Type 1 and Type 2 plasminogen by Type I and Type II tissue plasminogen activator. Biochem. J. 270, 3261-3267. doi: 10.1074/jbc.270.7.3261
79. Ng, K. S., Leung, H. W., Wong, P. T. H., and Low, C. M. (2012). Cleavage of the NR2B subunit amino terminus of N-methyl-D-aspartate (n.d.) Receptor by tissue plasminogen activator: identification of the cleavage site and characterization of ifenprodil and glycine affinities on truncated NMDA receptor. J. Biol. Chem. 287, 25520-25529. doi: 10.1074/jbc.M112.374397
80. Nicole, O., Docagne, F., Ali, C., Margaill, I., Carmeliet, P., MacKenzie, E. T., et al. (2001). The proteolytic activity of tissue-plasminogen activator enhances NMDA receptor-mediated signaling. Nat. Med. 7, 59-64. doi: 10.1038/83358
81. NINDS (1995). Tissue plasminogen activator for acute ischemic stroke. N. Engl. J. Med. 333, 1581-1587. doi: 10.1056/NEJM199512143332401
82. Omouendze, P. L., Henry, V. J., Porte, B., Dupré, N., Carmeliet, P., Gonzalez, B. J., et al. (2013). Hypoxia-ischemia or excitotoxin-induced tissue plasminogen activator- dependent gelatinase activation in mice neonate brain microvessels. PLoS ONE 8:e71263. doi: 10.1371/journal.pone.0071263
83. Ortiz-Zapater, E., Peiró, S., Roda, O., Corominas, J. M., Aguilar, S., Ampurdanés, C., et al. (2007). Tissue plasminogen activator induces pancreatic cancer cell proliferation by a non-catalytic mechanism that requires extracellular signal-regulated kinase 1/2 activation through epidermal growth factor receptor and annexin A2. Am. J. Pathol. 170, 1573-1584. doi: 10.2353/ajpath.2007.060850
84. Pang, P. T., Teng, H. K., Zaitsev, E., Woo, N. T., Sakata, K., Zhen, S., et al. (2004). Cleavage of proBDNF by tPA/plasmin is essential for long-term hippocampal plasticity. Science 306, 487-491. doi: 10.1126/science.1100135
85. Paoletti, P., Bellone, C., and Zhou, Q. (2013). NMDA receptor subunit diversity: impact on receptor properties, synaptic plasticity and disease. Nat. Rev. Neurosci. 14, 383-400. doi: 10.1038/nrn3504
86. Parcq, J., Bertrand, T., Montagne, A., Baron, A. F., Macrez, R., Billard, J. M., et al. (2012). Unveiling an exceptional zymogen: the single-chain form of tPA is a selective activator of NMDA receptor-dependent signaling and neurotoxicity. CellDeath. Differ. 19, 1983-1991. doi: 10.1038/cdd.2012.86
87. Park, L., Gallo, E. F., Anrather, J., Wang, G., Norris, E. H., Paul, J., et al. (2008). Key role of tissue plasminogen activator in neurovascular coupling. Proc. Natl. Acad. Sci. U.S.A. 105, 1073-1078. doi: 10.1073/pnas.0708823105
88. Pawlak, R., Nagai, N., Urano, T., Napiorkowska-Pawlak, D., Ihara, H., Takada, Y., et al. (2002). Rapid, specific and active site-catalyzed effect of tissue-plasminogen activator on hippocampus-dependent learning in mice. Neuroscience 113, 995-1001. doi: 10.1016/S0306-4522(02)00166-5
89. Pennica, D., Holmes, W. E., Kohr, W. J., Harkins, R. N., Vehar, G. A., Ward, C. A., et al. (1983). Cloning and expression of human tissue-type plasminogen activator cDNA in E. coli. Nature 301, 214-221. doi: 10.1038/301214a0
90. Petersen, L. C., Johannessen, M., Foster, D., Kumar, A., and Mulvihill, E. (1988). The effect of polymerised fibrin on the catalytic activities of one- chain tissue-type plasminogen activator as revealed by an analogue resistant to plasmin cleavage. Biochim. Biophys. Acta 952, 245-254. doi: 10.1016/0167-4838(88)90123-9
91. Pineda, D., Ampurdanés, C., Medina, M. G., Serratosa, J., Tusell, J. M., Saura, J., et al. (2012). Tissue plasminogen activator induces microglial inflammation via a noncatalytic molecular mechanism involving activation of mitogen-activated protein kinases and Akt signaling pathways and AnnexinA2 and Galectin-1 receptors. Glia 60, 526-540. doi: 10.1002/glia.22284
92. Pohl, G., Källström, M., Bergsdorf, N., Wallén, P., and Jörnvall, H. (1984). Tissue plasminogen activator: peptide analyses confirm an indirectly derived amino acid sequence, identify the active site serine residue, establish glycosylation sites, and localize variant differences. Biochemistry 23, 3701-3707. doi: 10.1021/bi00311a020
93. Polavarapu, R., Gongora, M. C., Yi, H., Ranganthan, S., Lawrence, D. A., Strickland, D., et al. (2007). Tissue-type plasminogen activator - mediated shedding of astrocytic low-density lipoprotein receptor - related protein increases the permeability of the neurovascular unit. Blood 109, 3270-3278. doi: 10.1182/blood-2006-08-043125
94. Rånby, M., Bergsdorf, N., and Nilsson, T. (1982). Enzymatic properties of the one- and two-chain form of tissue plasminogen activator. Thromb. Res. 27, 175-183. doi: 10.1016/0049-3848(82)90197-9
95. Rathore, Y. S., Rehan, M., Pandey, K., and Ashish, S. G. (2012). First structural model of full-length human tissue-plasminogen activator: a SAXS data- based modeling study. J. Phys. Chem. B. 116, 496-502. doi: 10.1021/ jp207243n
96. Reddrop, C., Moldrich, R. X., Beart, P. M., Farso, M., Liberatore, G. T., Howells, D. W., et al. (2005). Vampire bat salivary plasminogen activator (desmoteplase) inhibits tissue-type plasminogen activator-induced potentiation of excitotoxic injury. Stroke 36, 1241-1246. doi: 10.1161/01.STR.0000166050.84056.48
97. Rijken, D. C., Wijngaards, G., Jong, M. Z., and Welbergen, J. (1979). Purification and partial characterization of plasminogen activator from human uterine tissue. Biochim. Biophys. Acta 580, 140-153. doi: 10.1016/0005-2795(79) 90205-8
98. Rodríguez-González, R., Agulla, J., Pérez-Mato, M., Sobrino, T., and Castillo, J. . Neuroprotective effect of neuroserpin in rat primary cortical cultures after oxygen and glucose deprivation and tPA. Neurochem. Int. 58, 337-343. doi: 10.1016/j.neuint.2010.12.006
99. Roussel, B. D., Macrez, R., Jullienne, A., Agin, V., Maubert, E., Dauphinot, L., et al. (2009). Age and albumin D site-binding protein control tissue plasminogen activator levels: neurotoxic impact. Brain 132, 2219-2230. doi: 10.1093/brain/awp162
100. Roussel, B. D., Mysiorek, C., Rouhiainen, A., Jullienne, A., Parcq, J., Hommet, Y., et al. (2011). HMGB-1 promotes fibrinolysis and reduces neurotoxicity mediated by tissue plasminogen activator. J. Cell Sci. 124, 2070-2076. doi: 10.1242/jcs.084392
101. Samson, A. L., Nevin, S. T., Croucher, D., Niego, B., Daniel, P. B., Weiss, T. W., et al.; Tissue-type plasminogen activator requires a co-receptor to enhance NMDA receptor function. J. Neurochem. 107, 1091-1101. doi: 10.1111/j.1471-4159.2008.05687.x
102. Shi, R., Weng, J., Zhao, L., Li, X. M., Gao, T. M., and Kong, J. (2012). Excessive autophagy contributes to neuron death in cerebral ischemia. CNS Neurosci. Ther. 18, 250-260. doi: 10.1111/j.1755-5949.2012.00295.x
103. Siao, C. J., and Tsirka, S. E. (2002). Tissue plasminogen activator mediates microglial activation via its finger domain through annexin II. J. Neurosci. 22, 3352-3358.
104. Siddiq, M. M., and Tsirka, S. E. (2004). Modulation of zinc toxicity by tissue plasminogen activator. Mol. Cell. Neurosci. 25, 162-171. doi: 10.1016/j.mcn.2003.10.007
105. Spellman, M. W., Basa, L. J., Leonard, C. K., Chakel, J. A., O'Connor, J. V., Wilson, S., et al. (1989). Carbohydrate structures of human tissue plasminogen activator expressed in Chinese hamster ovary cells. J. Biol. Chem. 264, 14100-14111.
106. Sun, H. Y., Szlam, F., Levy, J. H., Csete, M. E., and Tanaka, K. A. (2009). Antifibrinolytic agents reduce tissue plasminogen activator-mediated neuronal toxicity in vitro. Acta Anaesthesiol. Scand. 53, 325-331. doi: 10.1111/j.1399-6576.2008.01858.x
107. Tate, K. M., Higgins, D. L., Holmes, W. E., Winkler, M. E., Heyneke, H. L., and Vehar, G. A. (1987). Functional role of proteolytic cleavage at arginine-275 of human tissue plasminogen activator as assessed by site-directed mutagenesis. Biochemistry 26, 338-343. doi: 10.4049/jimmunol.1100412
108. Terro, F., Esclaire, F., Yardin, C., and Hugon, J. (2000). N-methyl-D-aspartate receptor blockade enhances neuronal apoptosis induced by serum deprivation. Neurosci. Lett. 278, 149-152. doi: 10.1016/S0304-3940(99)00911-8
109. Thelwell, C., and Longstaff, C. (2007). The regulation by fibrinogen and fibrin of tissue plasminogen activator kinetics and inhibition by plasminogen activator inhibitor 1. J. Thromb. Haemost. 5, 804-811. doi: 10.1111/j.1538-7836.2007.02422.x
110. Tsirka, S. E., Bugge, T. H., Degen, J. L., and Strickland, S. (1997a). Neuronal death in the central nervous system demonstrates a non-fibrin substrate for plasmin. Proc. Natl. Acad. Sci. U.S.A. 94, 9779-9781. doi: 10.1073/pnas.94.18.9779
111. Tsirka, S. E., Rogove, A. D., Bugge, T. H., Degen, J. L., and Strickland, S. (1997b). An extracellular proteolytic cascade promotes neuronal degeneration in the mouse hippocampus. J. Neurosci. 17, 543-552.
112. Tsirka, S. E., Gualandris, A., Amaral, D. G., and Strickland, S. (1995). Excitotoxin- induced neuronal degeneration and seizure are mediated by tissue plasminogen activator. Nature 377, 340-344. doi: 10.1038/377340a0
113. Tucker, H. M., Kihiko, M., Caldwell, J. N., Wright, S., Kawarabayashi, T., Price, D., et al. (2000). The plasmin system is induced by and degrades amyloid-beta aggregates. J. Neurosci. 20, 3937-3946.
114. Vandenberghe, W., Van Den Bosch, L., and Robberecht, W. (1998). Tissue-type plasminogen activator is not required for kainate-induced motoneuron death in vitro. Neuroreport 9, 2791-2796. doi: 10.1097/00001756-199808240-00020
115. Wallén, P., Bergsdorf, N., and Rånby, M. (1982). Purification and identification of two structural variants of porcine tissue plasminogen activator by affinity adsorption on fibrin. Biochim. Biophys. Acta 719, 318-328. doi: 10.1016/0304-4165(82)90105-2
116. Wang, X., Asahi, M., and Lo, E. H. (1999). Tissue type plasminogen activator amplifies hemoglobin-induced neurotoxicity in rat neuronal cultures. Neurosci. Lett. 274, 79-82. doi: 10.1016/S0304-3940(99)00682-5
117. Wang, Y. F., Tsirka, S. E., Strickland, S., Stieg, P. E., Soriano, S. G., and Lipton, S. A. (1998). Tissue plasminogen activator (tPA) increases neuronal damage after focal cerebral ischemia in wild-type and tPA-deficient mice. Nat. Med. 4, 228-231. doi: 10.1038/ng0598-56
118. Wiegler, K., Bonny, C., Coquoz, D., and Hirt, L. (2008). The JNK inhibitor XG-102 protects from ischemic damage with delayed intravenous administration also in the presence of recombinant tissue plasminogen activator. Cerebrovasc. Dis. 26, 360-366. doi: 10.1159/000151639
119. Wittwer, A. J., and Howard, S. C. (1990). Glycosylation at Asn-184 inhibits the conversion of single-chain to two-chain tissue-type plasminogen activator by plasmin. Biochemistry 29, 4175-4180. doi: 10.1021/bi00469a021
120. Wittwer, A. J., Howard, S. C., Carr, L. S., Harakas, N. K., Feder, J., Parekh, R. B., et al. (1989). Effects of N-glycosylation on in vitro activity of Bowes melanoma and human colon fibroblast derived tissue plasminogen activator. Biochemistry 28, 7662-7669. doi: 10.1021/bi00445a022
121. Wu, F., Echeverry, R., Wu, J., An, J., Haile, W. B., Cooper, D. S., et al. (2013a). Tissue-type plasminogen activator protects neurons from excitotoxin-induced cell death via activation of the ERK1/2-CREB-ATF3 signaling pathway. Mol. Cell. Neurosci. 52, 9-19. doi: 10.1016/j.mcn.2012.10.001
122. Wu, F., Nicholson, A. D., Haile, W. B., Torre, E., An, J., Chen, C., et al. (2013b). Tissue-type plasminogen activator mediates neuronal detection and adaptation to metabolic stress. J. Cereb. Blood Flow Metab. 33, 1761-1769. doi: 10.1038/jcbfm.2013.124
123. Wu, F., Wu, J., Nicholson, A. D., Echeverry, R., Haile, W. B., Tong, F. C., et al. (2012). Tissue-type plasminogen activator regulates the neuronal uptake of glucose in the ischemic brain. J. Neurosci. 32, 9848-9858. doi: 10.1523/JNEUROSCI.1241-12.2012
124. Yi, J. S., Kim, Y. H., and Koh, J. Y. (2004). Infarct reduction in rats following intraventricular administration of either tissue plasminogen activator (tPA) or its non-protease mutant S478A-tPA. Exp. Neurol. 189, 354-360. doi: 10.1016/j.expneurol.2004.05.032
125. Yuan, H., Vance, K. M., Junge, C. E., Geballe, M. T., Snyder, J. P., Hepler, J. R., et al. . The serine protease plasmin cleaves the amino-terminal domain of the NR2A subunit to relieve zinc inhibition of the N-methyl-D-aspartate receptors. J. Biol. Chem. 284, 12862-12873. doi: 10.1074/jbc.M805123200
126. Zhang, Z., Zhang, L., Yepes, M., Jiang, Q., Li, Q., Arniego, P., et al. (2002). Adjuvant treatment with neuroserpin increases the therapeutic window for tissue-type plasminogen activator administration in a rat model of embolic stroke. Circulation 106, 740-745. doi: 10.1161/01.CIR.0000023942.10849.41