| RRC ID |
12448
|
| Author |
Kimura M, Soeda S, Oda M, Ochiai T, Kihara T, Ono N, Shimeno H.
|
| Title |
Release of plasminogen activator inhibitor-1 from human astrocytes is regulated by intracellular ceramide.
|
| Journal |
J Neurosci Res
|
| Abstract |
The present study underscores a regulatory role of intracellular ceramide in astrocytes for the release of an extracellular serine protease, tissue-type plasminogen activator (t-PA), and its inhibitor, plasminogen activator inhibitor-1 (PAI-1). Treatment of cultured human astrocytes with N-acetylsphingosine, a cell-permeable short-chain ceramide analogue or daunorubicin that could increase intracellular ceramide via activation of ceramide synthase or sphingomyelin hydrolysis increased the release of t-PA and conversely decreased the PAI-1 release. Interestingly, treatment of the astrocytes with tumor necrosis factor (TNF)-alpha also increased the intracellular ceramide levels but caused the elevation of PAI-1 release without altering the t-PA release. These data suggest that the generation of ceramide in astrocytes is linked at least with the regulation of PAI-1 release. We also demonstrate that the suppression of PAI-1 release with daunorubicin accelerates the cell death of neuronally differentiated PC12 cells and suggest an antiapoptotic role of PAI-1 in the nervous system.
|
| Volume |
62(6)
|
| Pages |
781-8
|
| Published |
2000-12-15
|
| DOI |
10.1002/1097-4547(20001215)62:6<781::AID-JNR4>3.0.CO;2-W
|
| PII |
10.1002/1097-4547(20001215)62:6<781::AID-JNR4>3.0.CO;2-W
|
| PMID |
11107162
|
| MeSH |
Animals
Antibiotics, Antineoplastic / pharmacology
Astrocytes / drug effects
Astrocytes / metabolism*
Cell Death / drug effects
Cell Death / physiology
Ceramides / metabolism*
Culture Media, Conditioned / pharmacology
Daunorubicin / pharmacology
Enzyme Inhibitors / pharmacology
Humans
Neurons / drug effects
Neurons / metabolism
PC12 Cells
Plasminogen Activator Inhibitor 1 / metabolism*
Rats
Sphingosine / analogs & derivatives
Sphingosine / pharmacology
Tissue Plasminogen Activator / drug effects
Tissue Plasminogen Activator / metabolism*
Tumor Necrosis Factor-alpha / pharmacology
|
| Times Cited |
39
|
|
WOS Category
|
MEDICINE, RESEARCH & EXPERIMENTAL
ENDOCRINOLOGY & METABOLISM
|
| Resource |
| Human and Animal Cells |
PC-12(RCB0009) |
