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http://dx.doi.org/10.4062/biomolther.2012.102

Transcriptional Upregulation of Plasminogen Activator Inhibitor-1 in Rat Primary Astrocytes by a Proteasomal Inhibitor MG132  

Cho, Kyu Suk (Department of Neuroscience, School of Medicine, Konkuk University)
Kwon, Kyoung Ja (Department of Neurology, School of Medicine, Konkuk University)
Jeon, Se Jin (Department of Neuroscience, School of Medicine, Konkuk University)
Joo, So Hyun (SMART Institute of Advanced Biomedical Science, Konkuk University)
Kim, Ki Chan (Department of Neuroscience, School of Medicine, Konkuk University)
Cheong, Jae Hoon (Department of Pharmacy, Sahmyook University)
Bahn, Geon Ho (Department of Neuropsychiatry, School of Medicine, Kyung Hee University)
Kim, Hahn Young (Department of Neurology, School of Medicine, Konkuk University)
Han, Seol Heui (Department of Neurology, School of Medicine, Konkuk University)
Shin, Chan Young (Department of Neuroscience, School of Medicine, Konkuk University)
Yang, Sung-Il (Department of Pharmacology, School of Medicine, Konkuk University)
Publication Information
Biomolecules & Therapeutics / v.21, no.2, 2013 , pp. 107-113 More about this Journal
Abstract
Plasminogen activator inhibitor-1 (PAI-1) is a member of serine protease inhibitor family, which regulates the activity of tissue plasminogen activator (tPA). In CNS, tPA/PAI-1 activity is involved in the regulation of a variety of cellular processes such as neuronal development, synaptic plasticity and cell survival. To gain a more insights into the regulatory mechanism modulating tPA/PAI-1 activity in brain, we investigated the effects of proteasome inhibitors on tPA/PAI-1 expression and activity in rat primary astrocytes, the major cell type expressing both tPA and PAI-1. We found that submicromolar concentration of MG132, a cell permeable peptide-aldehyde inhibitor of ubiquitin proteasome pathway selectively upregulates PAI-1 expression. Upregulation of PAI-1 mRNA as well as increased PAI-1 promoter reporter activity suggested that MG132 transcriptionally increased PAI-1 expression. The induction of PAI-1 downregulated tPA activity in rat primary astrocytes. Another proteasome inhibitor lactacystin similarly increased the expression of PAI-1 in rat primary astrocytes. MG132 activated MAPK pathways as well as PI3K/Akt pathways. Inhibitors of these signaling pathways reduced MG132-mediated upregulation of PAI-1 in varying degrees and most prominent effects were observed with SB203580, a p38 MAPK pathway inhibitor. The regulation of tPA/PAI-1 activity by proteasome inhibitor in rat primary astrocytes may underlie the observed CNS effects of MG132 such as neuroprotection.
Keywords
MG132; Lactacystin; p38; Plasminogen activator inhibitor-1; Tissue plasminogen activator;
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1 Docagne, F., Nicole, O., Gabriel, C., Fernandez-Monreal, M., Lesne, S., Ali, C., Plawinski, L., Carmeliet, P., MacKenzie, E. T., Buisson, A. and Vivien, D. (2002) Smad3-dependent induction of plasminogen activator inhibitor-1 in astrocytes mediates neuroprotective activity of transforming growth factor-${\beta}$eta 1 against NMDA-induced necrosis. Mol. Cell. Neurosci. 21, 634-644.   DOI   ScienceOn
2 Doller, A., Gauer, S., Sobkowiak, E., Geiger, H., Pfeilschifter, J. and Eberhardt, W. (2009) Angiotensin II induces renal plasminogen activator inhibitor-1 and cyclooxygenase-2 expression post-transcriptionally via activation of the mRNA-stabilizing factor human-antigen R. Am. J. Pathol. 174, 1252-1263.   DOI   ScienceOn
3 Duan, W., Guo, Y., Jiang, H., Yu, X. and Li, C. (2011) MG132 enhances neurite outgrowth in neurons overexpressing mutant TAR DNA-binding protein-43 via increase of HO-1. Brain. Res. 1397, 1-9.   DOI   ScienceOn
4 Giasson, B. I., Bruening, W., Durham, H. D. and Mushynski, W. E. (1999) Activation of stress-activated protein kinases correlates with neurite outgrowth induced by protease inhibition in PC12 cells. J. Neurochem. 72, 1081-1087.
5 Guo, N. and Peng, Z. (2012) MG132, a proteasome inhibitor, induces apoptosis in tumor cells. Asia Pac. J. Clin. Oncol. [Epub ahead of print]
6 Higgins, P. J. (2006) The TGF-beta1/upstream stimulatory factor-regulated PAI-1 gene: potential involvement and a therapeutic target in Alzheimer's disease. J. Biomed. Biotechnol. 2006, 15792.
7 Hultman, K., Blomstrand, F., Nilsson, M., Wilhelmsson, U., Malmgren, K., Pekny, M., Kousted, T., Jern, C. and Tjarnlund-Wolf, A. (2010) Expression of plasminogen activator inhibitor-1 and protease nexin-1 in human astrocytes: Response to injury-related factors. J. Neurosci. Res. 88, 2441-2449.
8 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. and Shin, C. Y. (2011) 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.   DOI   ScienceOn
9 Baranes, D., Lederfein, D., Huang, Y. Y., Chen, M., Bailey, C. H. and Kandel, E. R. (1998) Tissue plasminogen activator contributes to the late phase of LTP and to synaptic growth in the hippocampal mossy fiber pathway. Neuron 21, 813-825.   DOI   ScienceOn
10 Woo, K. J., Park, J. W. and Kwon, T. K. (2006) Proteasome inhibitor-induced cyclooxygenase-2 expression in Raw264.7 cells is potentiated by inhibition of c-Jun N-terminal kinase activation. Biochem. Biophys. Res. Commun. 342, 1334-1340.   DOI   ScienceOn
11 Wu, H. M., Chi, K. H. and Lin, W. W. (2002a) Proteasome inhibitors stimulate activator protein-1 pathway via reactive oxygen species production. FEBS Lett. 526, 101-105.   DOI   ScienceOn
12 Wu, H. M., Wen, H. C. and Lin, W. W. (2002b) Proteasome inhibitors stimulate interleukin-8 expression via Ras and apoptosis signal-regulating kinase-dependent extracellular signal-related kinase and c-Jun N-terminal kinase activation. Am. J. Respir. Cell Mol. Biol. 27, 234-243.   DOI   ScienceOn
13 Wu, Y. P., Siao, C. J., Lu, W., Sung, T. C., Frohman, M. A., Milev, P., Bugge, T. H., Degen, J. L., Levine, J. M., Margolis, R. U. and Tsirka, S. E. (2000) The tissue plasminogen activator (tPA)/plasmin extracellular proteolytic system regulates seizure-induced hippocampal mossy fiber outgrowth through a proteoglycan substrate. J. Cell Biol. 148, 1295-1304.   DOI
14 Zhang, Y., Kanaho, Y., Frohman, M. A. and Tsirka, S. E. (2005) Phospholipase D1-promoted release of tissue plasminogen activator facilitates neurite outgrowth. J. Neurosci. 25, 1797-1805.   DOI   ScienceOn
15 LeBel, C. P., Ali, S. F., McKee, M. and Bondy, S. C. (1990) Organometal-induced increases in oxygen reactive species: the potential of 2',7'-dichlorofluorescin diacetate as an index of neurotoxic damage. Toxicol. Appl. Pharmacol. 104, 17-24.   DOI   ScienceOn
16 Oh, C. J., Kim, J. Y., Min, A. K., Park, K. G., Harris, R. A., Kim, H. J. and Lee, I. K. (2012) Sulforaphane attenuates hepatic fibrosis via NF-E2-related factor 2-mediated inhibition of transforming growth factor-${\beta}$/Smad signaling. Free. Radic. Biol. Med. 52, 671-682.   DOI   ScienceOn
17 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. and Shin, C. Y. (2008) 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.   DOI   ScienceOn
18 Masos, T. and Miskin, R. (1997) mRNAs encoding urokinase-type plasminogen activator and plasminogen activator inhibitor-1 are elevated in the mouse brain following kainate-mediated excitation. Brain. Res. Mol. Brain. Res. 47, 157-169.   DOI   ScienceOn
19 Nakayama, K., Furusu, A., Xu, Q., Konta, T. and Kitamura, M. (2001) Unexpected transcriptional induction of monocyte chemoattractant protein 1 by proteasome inhibition: involvement of the c-Jun N-terminal kinase-activator protein 1 pathway. J. Immunol. 167, 1145-1150.   DOI
20 Rachakonda, G., Sekhar, K. R., Jowhar, D., Samson, P. C., Wikswo, J. P., Beauchamp, R. D., Datta, P. K. and Freeman, M. L. (2010) Increased cell migration and plasticity in Nrf2-deficient cancer cell lines. Oncogene 29, 3703-3714.   DOI   ScienceOn
21 Sahni, S. K., Rydkina, E. and Sahni, A. (2008) The proteasome inhibitor MG132 induces nuclear translocation of erythroid transcription factor Nrf2 and cyclooxygenase-2 expression in human vascular endothelial cells. Thromb. Res. 122, 820-825.   DOI   ScienceOn
22 Seeds, N. W., Basham, M. E. and Haffke, S. P. (1999) Neuronal migration is retarded in mice lacking the tissue plasminogen activator gene. Proc. Natl. Acad. Sci. USA 96, 14118-14123.   DOI
23 Song, E. J. and Yoo, Y. S. (2011) Nerve growth factor-induced neurite outgrowth is potentiated by stabilization of TrkA receptors. BMB Rep. 44, 182-186.   DOI   ScienceOn
24 Shin, C. Y., Choi, J. W., Ryu, J. R., Ryu, J. H., Kim, W., Kim, H. and Ko, K. H. (2001) Immunostimulation of rat primary astrocytes decreases intracellular ATP level. Brain. Res. 902, 198-204.   DOI   ScienceOn
25 Shin, C. Y., Kundel, M. and Wells, D. G. (2004) Rapid, activity-induced increase in tissue plasminogen activator is mediated by metabotropic glutamate receptor-dependent mRNA translation. J. Neurosci. 24, 9425-9433.   DOI   ScienceOn
26 Song, E. J., Hong, H. M. and Yoo, Y. S. (2009) Proteasome inhibition induces neurite outgrowth through posttranslational modification of TrkA receptor. Int. J. Biochem. Cell Biol. 41, 539-545.   DOI   ScienceOn
27 Chen, J. J., Huang, W. C. and Chen, C. C. (2005) Transcriptional regulation of cyclooxygenase-2 in response to proteasome inhibitors involves reactive oxygen species-mediated signaling pathway and recruitment of CCAAT/enhancer-binding protein delta and CREB-binding protein. Mol. Biol. Cell 16, 5579-5591.   DOI   ScienceOn
28 Cho, I. J., Kim, S. H. and Kim, S. G. (2006) Inhibition of TGFbeta1-mediated PAI-1 induction by oltipraz through selective interruption of Smad 3 activation. Cytokine 35, 284-294.   DOI   ScienceOn
29 Cho, K. S., Park, S. H., Joo, S. H., Kim, S. H. and Shin, C. Y. (2010) The effects of IL-32 on the inflammatory activation of cultured rat primary astrocytes. Biochem. Biophys. Res. Commun. 402, 48-53.   DOI   ScienceOn
30 Czekay, R. P., Wilkins-Port, C. E., Higgins, S. P., Freytag, J., Overstreet, J. M., Klein, R. M., Higgins, C. E., Samarakoon, R. and Higgins, P. J. (2011) PAI-1: An integrator of cell signaling and migration. Int. J. Cell Biol. 2011, 562481.