Download PDF
Thromb Haemost 2008; 100(06): 1014-1020
DOI: 10.1160/TH08-04-0259
Theme Issue Article
Schattauer GmbH

Anti-apoptotic roles of plasminogen activator inhibitor-1 as a neurotrophic factor in the central nervous system

Shinji Soeda
1   Department of Biochemistry, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan
,
Satoru Koyanagi
2   Pharmaceutics, Division of Clinical Pharmacy, Department of Medico-Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan
,
Yukako Kuramoto
1   Department of Biochemistry, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan
,
Masahiko Kimura
3   Medical Informatics and Research Units, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan
,
Masatoshi Oda
1   Department of Biochemistry, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan
,
Tomohiro Kozako
1   Department of Biochemistry, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan
,
Satoru Hayashida
1   Department of Biochemistry, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan
,
Hiroshi Shimeno
1   Department of Biochemistry, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan
› Author AffiliationsFinancial support: This work was supported in part by a Grant-in-Aid for Scientific Research I from the Ministry of Education, Science, Sports and Culture of Japan and by funds from Central Research Institute of Fukuoka University and from MEXT HAITEKU (2002-6).
Further Information

Publication History

Received: 24 April 2008

Accepted after minor revision: 02 September 2008

Publication Date:
23 November 2017 (online)

Also available at
    Permissions and Reprints

Summary

Plasminogen activator inhibitor-1 (PAI-1), a member of the ser-pin gene family, is the primary inhibitor of urokinase-type and tissue-type PA s.PA I-1 plays an important role in the process of peripheral tissue remodeling and fibrinolysis through the regulation of PA activity. This serpin is also produced in brain tissues and may regulate the neural protease sequence in the central nervous system (CNS), as it does in peripheral tissues. In fact, PA I-1 mRNA is up-regulated in mouse brain after stroke.The serpin activity of PA I-1 helps to prevent tissue-type PA -induced neuron death.However, we have previously found that PAI-1 has a novel biological function in the CNS: the contribution to survival of neurites on neurons. In neuronally differentiated rat pheochromocytoma (PC-12) cells, a deficiency of PA I-1 in vitro caused a significant reduction in Bcl-2 and Bcl-XL mRNAs and an increase in Bcl-XS and Bax mRNAs.The change in the balance between mRNA expressions of the anti- and pro-apoptotic Bcl-2 family proteins promoted the apoptotic sequence: cas-pase-3 activation, cytochrome c release from mitochondria and DNA fragmentation. Our results indicate that PA I-1 has an antiapoptotic role in neurons.PAI-1 prevented the disintegration of the formed neuronal networks by maintaining or promoting neuroprotective signaling through the MAPK/ ERK pathway, suggesting that the neuroprotective effect of PAI-1 is independent of its action as a protease inhibitor. This review discusses the neuroprotective effects of PA I-1 in vitro, together with the relevant data from other laboratories. Special emphasis is placed on its action on PC-12 cells.

Keywords

Plasminogen activator inhibitor-1 - neurotrophic factor - ERKrelated pathway - astrocytes - PC-12 cells
 

  • References

  • 1 Margaglione M, Di Minno G, Grandone E. et al. Abnormally high circulation levels of tissue plasminogen activator and plasminogen activator in-hibitor-1 in patients with a history of ischemic stroke. Arterioscler Thromb 1994; 14: 1741-1745.
    CrossrefPubMedSearch in Google Scholar
  • 2 Meade TW, Ruddock V, Stirling Y. et al. Fibrinolytic activity, clotting factors, and long-term incidence of ischemic heart disease in the Northwick Park Heart Study. Lancet 1993; 342: 1076-1079.
    CrossrefPubMedSearch in Google Scholar
  • 3 Juhan-Vague I, Vague P, Alessi MC. et al. Relationships between plasma insulin, triglyceride, body mass index, and plasminogen activator inhibitor-1. Diabetes Metab 1987; 13: 331-336.
    PubMedSearch in Google Scholar
  • 4 Morange PE, Alessi MC, Verdier M. et al. PAI-1 produced ex vivo by human adipose tissue is relevant to PA I-1 blood level. Arterioscler Thromb Vasc Biol 1999; 19: 1361-1365.
    CrossrefPubMedSearch in Google Scholar
  • 5 Alessi MC, Peiretti F, Morange P. et al. Production of plasminogen activator inhibitor 1 by human adipose tissue - possible link between visceral fat accumulation and vascular disease. Diabetes 1997; 46: 860-867.
    CrossrefPubMedSearch in Google Scholar
  • 6 Birgel M, Gottschling-Zeller H, Rohrig K. et al. Role of cytokines in the regulation of plasminogen activator inhibitor 1 expression and secretion in newly differentiated subcutaneous human adipocytes. Arterioscler Thromb Vasc Biol 2000; 20: 1682-1687.
    CrossrefPubMedSearch in Google Scholar
  • 7 Alessi MC, Bastelica D, Morange P. et al. Plasminogen activator inhibitor 1, transforming growth factor-β1, and BMI are closely associated in human adipose tissue during morbid obesity. Diabetes 2000; 49: 1374-1380.
    CrossrefPubMedSearch in Google Scholar
  • 8 Zirlik A, Leugers A, Lohrmann J. et al. Direct attenuation of plasminogen activator inhibitor type-1 expression in human adipose tissue by thiazolidine-diones. Thromb Haemost 2004; 91: 674-682.
    Thieme ConnectPubMedSearch in Google Scholar
  • 9 Murakami M, Ikeda T, Saito T. et al. Transcriptional regulation of plasminogen activator inhibitor-1 by transforming growth factor-β, activin A and micro-phthalmia-associated transcription factor. Cellular Signalling 2006; 18: 256-265.
    CrossrefPubMedSearch in Google Scholar
  • 10 Jiang Z, Seo JY, Ha H. et al. Reactive oxygen species mediate TGF-?1-induced plasminogen activator inhibitor-1 upregulation in mesangical cells. Biochem Biophys Res Commn 2003; 309: 961-966.
    CrossrefPubMedSearch in Google Scholar
  • 11 Buisson A, Nicole O, Docagne F. et al. Up-regulation of a serine protease inhibitor in astrocytes mediates the neuroprotective activity of transforming growth factor β1. FASEB J 1998; 12: 1683-1691.
    CrossrefPubMedSearch in Google Scholar
  • 12 Ahn MY, Zhang ZG, Tsang W. et al. Endogenous plasminogen activator expression after embolic focal cerebral ischemia in mice. Brain Res 1999; 837: 169-176.
    CrossrefPubMedSearch in Google Scholar
  • 13 Docagne F, Nicole O, Gabriel C. et al. Smad3-de-pendent induction of plasminogen activator inhibitor-1 in astrocytes mediates neuroprotective activity of transforming growth factor-β1 against NMDA-induced Necrosis. Mol Cell Neurosci 2002; 21: 634-644.
    CrossrefPubMedSearch in Google Scholar
  • 14 Takahashi H, Uno S, Watanabe Y. et al. Expression of nerve growth factor-induced type 1 plasminogen activator inhibitor (PA I-1) mRNA is inhibited by genis-tein and wortmannin. NeroReport 2000; 11: 1111-1115.
    PubMedSearch in Google Scholar
  • 15 Kimura M, Soeda S, Oda M. et al. Release of plasminogen activator inhibitor-1 from human astrocytes is regulated by intracellular ceramide. J Neurosci Res 2000; 62: 781-788.
    CrossrefPubMedSearch in Google Scholar
  • 16 Obeid LM, Linardic CM, Karolak LA. et al. Programmed cell death induced by ceramide. Science 1993; 259: 1769-1771.
    CrossrefPubMedSearch in Google Scholar
  • 17 Soeda S, Iwata K, Hosoda Y. et al. Daunorubicin attenuates tumor necrosis factor-?-induced biosynthesis of plasminogen activator inhibitor-1 in human umbilical vein endothelial cells. Biochim Biophys Acta 2001; 1538: 234-241.
    CrossrefPubMedSearch in Google Scholar
  • 18 Krystosek A, Seeds NM. Plasminogen activator release at the neuronal growth cone. Science 1981; 213: 1532-1534.
    CrossrefPubMedSearch in Google Scholar
  • 19 Pittman RN. Release of plasminogen activator and a calcium-dependent metallo-protease from cultured sympathetic and sensory neurons. Dev Biol 1985; 110: 91-101.
    CrossrefPubMedSearch in Google Scholar
  • 20 Qian Z, Gillbert ME, Colicos MA. et al. Tissue plasminogen activator is induced as an immediate-early gene during seizure kindling and long-term potentiation. Nature 1993; 361: 453-457.
    CrossrefPubMedSearch in Google Scholar
  • 21 Tsirka SE, Gualandris A, Amaral DG. et al. Excitot-oxin-induced neuronal degeneration and seizure are mediated by tissue plasminogen activator. Nature 1995; 377: 340-344.
    CrossrefPubMedSearch in Google Scholar
  • 22 Tsirka SE, Rogove AD, Strickland S. Neuronal cell death and tPA. Nature 1996; 384: 123-124.
    PubMedSearch in Google Scholar
  • 23 Krueger SR, Ghisu GP, Cinelli P. et al. Expression of neuroserpin, an inhibitor of tissue plasminogen activator, in the developing and adult nervous system of the mouse. J Neurosci 1997; 17: 8984-8996.
    CrossrefPubMedSearch in Google Scholar
  • 24 Osterwalder T, Contartese J, Stoeckli ET. et al. Neu-roserpin, an axonally secreted serine protease inhibitor. EMBO J 1996; 15: 2944-2953.
    PubMedSearch in Google Scholar
  • 25 Osterwalder T, Cinelli P, Baici A. et al. The axonally secreted serine protease inhibitor, neuroserpin, inhibits plasminogen activators and plasmin but not thrombin. J Biol Chem 1998; 273: 2312-2321.
    CrossrefPubMedSearch in Google Scholar
  • 26 Hastings GA, Coleman TA, Haudenschild CC. et al. Neuroserpin, a brain-associated inhibitor of tissue plasminogen activator is localized primarily in neurons: implication for the regulation of motor learning and neuronal survival. J Biol Chem 1997; 272: 33062-33067.
    CrossrefPubMedSearch in Google Scholar
  • 27 Rao JS, Rayford A, Morantz RA. et al. Increased levels of plasminogen activator inhibitor-1 (PA I-1) in human brain tumors. J Neurooncol 1993; 17: 215-221.
    CrossrefPubMedSearch in Google Scholar
  • 28 Soeda S, Oda M, Ochiai T. et al. Deficient release of plasminogen activator inhibitor-1 from astrocytes triggers apoptosis in neuronal cells. Mol Brain Res 2001; 91: 96-103.
    CrossrefPubMedSearch in Google Scholar
  • 29 Soeda S, Imatoh T, Ochiai T. et al. Plasminogen activator inhibitor-1 aids survival of neuritis on neurons derived from pheochromocytoma (PC-12) cells. NeuroReport 2004; 15: 855-858.
    CrossrefPubMedSearch in Google Scholar
  • 30 Nakajima A, Yamada K, Zou L-B. et al. Inertleu-kin-6 protects PC12 cells from 4-hydroxynonenal-in-duced cytotoxity by increasing intracellular glutathione levels. Free Rad Biol Med 2002; 32: 1324-1332.
    CrossrefPubMedSearch in Google Scholar
  • 31 Jin KM, Mao XO, Greenberg DA. Vascular endothelial growth factor: direct neuroprotective effect in in vitro ischemia. Proc Natl Acad Sci USA 2000; 97: 10242-10247.
    CrossrefPubMedSearch in Google Scholar
  • 32 Gunn-Moore FJ, Tavare JM. Progress toward understanding the molecular mechanisms of neurotrophic factor signaling. Cell Signal 1998; 10: 151-157.
    CrossrefPubMedSearch in Google Scholar
  • 33 Harper SJ, LoGrasso P. Signalling for survival and death in neurons: the role of stress-activated kinases, JNK and p38. Cell Signal 2001; 13: 299-310.
    CrossrefPubMedSearch in Google Scholar
  • 34 Creedon DJ, Johnson EM, Lawrence JC. Mitogen-activated protein kinase-independent pathways mediate the effects of nerve growth factor and cAMP on neuronal survival. J Biol Chem 1996; 271: 20713-20718.
    CrossrefPubMedSearch in Google Scholar
  • 35 Klesse LJ, Meyers KA, Marshall CJ. et al. Nerve growth factor induces survival and differentiation through two distinct signaling cascades in PC12 cells. Oncogene 1999; 18: 2055-2068.
    CrossrefPubMedSearch in Google Scholar
  • 36 Webb DJ, Thomas KS, Gonias SL. Plasminogen activator inhibitor 1 functions as a urokinase response modifier at the level of cell signaling and thereby promotes MCF-7 cell growth. J Cell Biol 2001; 152: 741-751.
    CrossrefPubMedSearch in Google Scholar
  • 37 Farias-Eisner R, Vician L, Reddy S. et al. Expression of the urokinase plasminogen activator receptor is transiently required during priming of PC12 cells in nerve growth factor-directed cellular differentiation. J Neurosci Res 2001; 63: 341-346.
    CrossrefPubMedSearch in Google Scholar
  • 38 Hino H, Akiyama H, Iseki E. et al. Immunohisto-chemical localization of plasminogen activator in-hibitor-1 in rat and human brain tissues. Neurosci Lett 2001; 297: 105-108.
    CrossrefPubMedSearch in Google Scholar
  • 39 Selkoe DJ. Clearing the brain’s amyloid cobwebs. Neuron 2001; 32: 177-180.
    CrossrefPubMedSearch in Google Scholar
  • 40 Kingston IB, Castro MJ, Anderson S. In vitro stimulation of tissue-type plasminogen activator by Alzheimer amyloid beta-peptide analogues. Nat Med 1995; 01: 138-142.
    CrossrefPubMedSearch in Google Scholar
  • 41 Tucker HM, Kihiko-Ehmann M, Wright S. et al. Tissue plasminogen activator requires plasminogen to modulate amyloid-beta neurotoxicity and deposition. J Neurochem 2000; 75: 2172-2177.
    CrossrefPubMedSearch in Google Scholar
  • 42 Melchor JP, Pawlak R, Strickland S. The tissue plasminogen activator-plasminogen proteolytic cascade accelerates amyloid-β (Aβ) degradation and in-hibitsA?-induced neurodegeneration. J Neurosci 2003; 23: 8867-8871.
    CrossrefPubMedSearch in Google Scholar
  • 43 Soeda S, Shinomiya K, Ochiai T. et al. Plasminogen activator inhibitor-1 aids nerve growth factor-induced differentiation and survival of pheochromocytoma cells by activating both the extracellular signal-regulated kinase and c-Jun pathways. Neuroscience 2006; 141: 101-108.
    CrossrefPubMedSearch in Google Scholar
  • 44 Estus S, Zaks WJ, Freeman RS. et al. Altered gene expression in neurons during programmed cell death: identification of c-Jun as necessary for neuronal apoptosis. J Cell Biol 1994; 127: 1717-1727.
    CrossrefPubMedSearch in Google Scholar
  • 45 Dragunow M, Xu R, Walton M. et al. c-Jun promotes neurite outgrowth and survival in PC12 cells. Mol Brain Res 2000; 83: 20-33.
    CrossrefPubMedSearch in Google Scholar
  • 46 Zhou F-Q, Walter MA, Sinder WD. Turning on the machine: genetic control of axon regeneration by c-Jun. Neuron 2004; 43: 1-4.
    CrossrefPubMedSearch in Google Scholar
  • 47 Takeda M, Kato H, Takamiya A. et al. Injury-specific expression of activating transcription factor-3 in retinal ganglion cells and its colocalized expression with phosphorylated c-Jun. Invest Ophthalmol Vis Sci 2000; 41: 2412-2421.
    PubMedSearch in Google Scholar
  • 48 Nakagomi S, Suzuki Y, Namikawa K. et al. Expression of the activating transcription factor 3 prevent c-Jun N-terminal kinase-induced neuronal death by promoting heat shock protein 27 expression and Akt activation. J Neurosci 2003; 23: 5187-5196.
    CrossrefPubMedSearch in Google Scholar
  • 49 Pearson AG, Gray CW, Pearson JF. et al. AT F3 enhances c-Jun-mediated neurite sprouting. Mol Brain Res 2003; 120: 38-45.
    CrossrefPubMedSearch in Google Scholar
  • 50 Lambert JC, Chartier-Harlin MC, Cottel D. et al. Is the LDL receptor-related protein involved in Alzheimer’ s disease?. Neurogenetics 1999; 02: 109-113.
    CrossrefPubMedSearch in Google Scholar
  • 51 Degryse B, Neels JG, Czekay R-P. et al. The low density lipoprotein receptor-related protein is a motogenic receptor for plasminogen activator inhibitor-1. J Biol Chem 2004; 279: 22595-22604.
    CrossrefPubMedSearch in Google Scholar