Induction of plasminogen activator inhibitor 1 biosynthesis by hyperthermia
| Autor: | Gabriela E. Bergonzelli, Egbert K. O. Kruithof |
|---|---|
| Rok vydání: | 1991 |
| Předmět: |
Hyperthermia
Carcinoma Hepatocellular Hot Temperature Transcription Genetic Physiology Fibrosarcoma Clinical Biochemistry Molecular Sequence Data Inflammation Biology chemistry.chemical_compound Plasminogen Activators Transcription (biology) medicine Tumor Cells Cultured Humans RNA Messenger Base Sequence Liver Neoplasms Cell Biology medicine.disease Molecular biology Urokinase-Type Plasminogen Activator Hsp70 Hep G2 Plasminogen Inactivators chemistry Cell culture Plasminogen activator inhibitor-1 Tissue Plasminogen Activator medicine.symptom |
| Zdroj: | Journal of cellular physiology. 148(2) |
| ISSN: | 0021-9541 |
| Popis: | Hyperthermia is a clinical sign of inflammation and constitutes in itself an adaptive defense mechanism. The fibrinolytic system, a highly regulated proteolytic system, is involved in inflammatory processes. Plasminogen activator inhibitor 1 (PAI-1) is the principal inhibitor of the two activators of the fibrinolytic system: tissue- and urokinase-type PAs (t-PA and u-PA). Our present paper provides the first evidence that hyperthermia can directly induce PAI-1. A moderate heat stress, sufficient to induce heat shock protein 70 mRNA approximately 100-fold, resulted in a two- to three-fold increase in functionally active PAI-1 in the conditioned medium of human HT-1080 fibrosarcoma and Hep G2 hepatoma cells. Exposure of these cells to 42 degrees C led to a similar two-fold and two- to five-fold induction of PAI-1 mRNA expression in HT-1080 and Hep G2 cells, respectively, as has been determined by using both oligo d(T) selected and total RNA preparations. These results suggest that the observed increase in PAI-1 accumulation is due to an induction of PAI-1 biosynthesis. Run-on transcription analysis indicates that the induction of PAI-1 biosynthesis by hyperthermia is mediated by a stimulation of PAI-1 gene transcription. No significant effect of hyperthermia was found on t-PA or u-PA at the level of antigen accumulation, mRNA, and gene transcription in human HT-1080 fibrosarcoma cells. These results point to an additional regulatory mechanism of fibrinolysis in the context of inflammation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text