Gess, Bernhard and Sandner, Peter and Kurtz, Armin (1996) Differential effects of kinase inhibitors on erythropoietin and vascular endothelial growth factor gene expression in rat hepatocytes. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 432 (3). pp. 426-432. ISSN 0031-6768, 1432-2013
Full text not available from this repository.Abstract
This study sought to investigate whether a common protein kinase activity is involved in the sequence of events by which oxygen controls the expression of the genes for erythropoietin (EPO) and for vascular endothelial growth factor (VEGF) in rat hepatocytes. To this end we examined the influence of the non-specific kinase inhibitor staurosporine and of the tyrosine kinase inhibitor genistein on EPO and VEGF mRNA levels in primary cultures of rat hepatocytes kept at either high (20% O-2) or low (1% O-2) oxygen tension. We found that 3 h of exposure to the low O-2 tension increased EPO mRNA levels about 20-fold and the three VEGF (-180, -164, -120) mRNA levels, an average, about fourfold. Staurosporine did not change EPO and VEGF mRNA levels at 20% O-2, but in a concentration-dependent manner, decreased EPO and VEGF mRNA at 1% O-2 with IC50 values of 30 nM. and 1000 nM, respectively. Tn the presence of 1% O-2, genistein decreased EPO mRNA and VEGF mRNA levels with IC50 values Of about 36 and 360 mu M, respectively. Although mRNA levels for glycerine aldehyde phosphatehydrogenase (GAPDH) were not changed, staurosporine and genistein inhibited uridine incorporation into total RNA with IC50 values of about 1 mu M and 100 mu M, respectively, Comparison with the transcription inhibitor actinomycin D suggested that the effects of both kinase inhibitors on VEGF mRNA but not on EPO mRNA levels could be attributed to the non-specific inhibition of transcription in hepatocytes. These findings suggest that a kinase activity Is specifically involved in the O-2-dependent control of EPO gene expression but not of VEGF gene expression in hepatocytes.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | INDUCIBLE FACTOR-I; PROTEIN-KINASE; MESSENGER-RNA; HYPOXIA; erythropoietin; vascular endothelial growth factor; hepatocytes; hypoxia; kinase inhibitors |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Armin Kurtz |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 05 Jul 2023 06:05 |
| Last Modified: | 05 Jul 2023 06:05 |
| URI: | https://pred.uni-regensburg.de/id/eprint/51626 |
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