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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2013.1
- 수록면
- 107 - 113 (7page)
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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.
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참고문헌 (30)
참고문헌 신청
Baranes, D. / 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
Chen, J. J. / 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
Cho, I. J. / 2006 / Inhibition of TGFbeta1-mediated PAI-1 induction by oltipraz through selective interruption of Smad 3 activation / Cytokine 35:284~294
Cho, K. S. / 2010 / The effects of IL-32 on the inflammatory activation of cultured rat primary astrocytes / Biochem. Biophys. Res. Commun 402:48~53
Czekay, R. P. / 2011 / PAI-1: An integrator of cell signaling and migration / Int. J. Cell Biol 2011:562481
Chen, J. J. / 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
Cho, I. J. / 2006 / Inhibition of TGFbeta1-mediated PAI-1 induction by oltipraz through selective interruption of Smad 3 activation / Cytokine 35:284~294
Cho, K. S. / 2010 / The effects of IL-32 on the inflammatory activation of cultured rat primary astrocytes / Biochem. Biophys. Res. Commun 402:48~53
Czekay, R. P. / 2011 / PAI-1: An integrator of cell signaling and migration / Int. J. Cell Biol 2011:562481
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