| RRC ID |
41404
|
| 著者 |
Soeda S, Oda M, Ochiai T, Shimeno H.
|
| タイトル |
Deficient release of plasminogen activator inhibitor-1 from astrocytes triggers apoptosis in neuronal cells.
|
| ジャーナル |
Brain Res Mol Brain Res
|
| Abstract |
Plasminogen activator inhibitor-1 (PAI-1) plays an important role in the processes of peripheral tissue remodeling and fibrinolysis through the regulation of plasminogen activation. We found that cultured human astrocytes efficiently released PAI-1, and that both mRNA expression and protein release of PAI-1 were suppressed by pretreatment of the cells with daunorubicin. To examine the role of PAI-1 in the nervous system, neuronally differentiated PC-12 cells (PC-12 neurons) were maintained in a PAI-1-deficient culture medium derived from daunorubicin-pretreated astrocytes. The deficiency of PAI-1 in the medium caused a significant reduction in Bcl-2 and Bcl-XL mRNAs and an increase in Bcl-XS and Bax mRNAs in PC-12 neurons at 3 h. The changes in balance between mRNA expressions of the anti- and pro-apoptotic Bcl-2 family proteins caused caspase-3 activation following the release of cytochrome c from mitochondria. Apoptotic morphological change and DNA fragmentation were also observed in the neuronal cells at 24 h. Addition of exogenous PAI-1 protein to the inhibitor-deficient medium blocked the apoptotic changes in PC-12 neurons. However, addition of PAI-1 antibodies to control medium caused similar apoptotic changes in PC-12 neurons. During the apoptotic processes, plasminogen activator (PA) activity in the PAI-1-deficient medium was as low as the control level. The present data suggest that PAI-1 has physiological functions other than its role as PA inhibitor for the survival of neurons.
|
| 巻・号 |
91(1-2)
|
| ページ |
96-103
|
| 公開日 |
2001-7-13
|
| DOI |
10.1016/s0169-328x(01)00133-4
|
| PII |
S0169328X01001334
|
| PMID |
11457496
|
| MeSH |
Animals
Antibiotics, Antineoplastic / pharmacology
Apoptosis / physiology*
Astrocytes / cytology
Astrocytes / drug effects
Astrocytes / metabolism*
Cells, Cultured
Daunorubicin / pharmacology
Extracellular Space / metabolism
Gene Expression / drug effects
Gene Expression / physiology
Humans
Neurons / cytology*
PC12 Cells
Plasminogen Activator Inhibitor 1 / genetics
Plasminogen Activator Inhibitor 1 / metabolism*
Proto-Oncogene Proteins / genetics
Proto-Oncogene Proteins c-bcl-2 / genetics
RNA, Messenger / analysis
Rats
bcl-2-Associated X Protein
bcl-X Protein
|
| 引用数 |
34
|
| リソース情報 |
| ヒト・動物細胞 |
PC-12(RCB0009) |
