Regulation of thromboxane A2 biosynthesis in platelet-free human monocytes and the possible role of polypeptide growth factor(s) in the induction of cyclooxygenase system
| Autor: | Giovanna Bartolini, Vittorio Tomasi, Franca Guerrini, Mariella Chiricolo, Marina Orlandi, Melihat Fidan, Luisa Minghetti, Claudio Franceschi |
|---|---|
| Rok vydání: | 1986 |
| Předmět: |
medicine.medical_specialty
Platelet-derived growth factor Thromboxane medicine.medical_treatment Indomethacin Biophysics Biochemistry Dinoprostone Monocytes ABO Blood-Group System Thromboxane A2 chemistry.chemical_compound Endocrinology Epidermal growth factor Internal medicine medicine Animals Humans Platelet Platelet-Derived Growth Factor Aspirin biology Prostaglandins E Growth factor Hydrogen-Ion Concentration Thromboxane B2 Kinetics Blood chemistry Prostaglandin-Endoperoxide Synthases Enzyme Induction Dactinomycin biology.protein Cattle Cyclooxygenase Prostaglandin E |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism. 876:486-493 |
| ISSN: | 0005-2760 |
| DOI: | 10.1016/0005-2760(86)90035-4 |
| Popis: | It has previously been shown that platelet-free human monocytes, when properly incubated in the presence of animal and human sera, became capable of producing large amounts of thromboxane A 2 and prostaglandin E 2 . The characteristics of these processes are reported here. Prostaglandin biosynthesis was time and cell concentration dependent; 24 h of incubation at 37°C and 0.5 · 10 6 cells per ml medium were found to give the most reproducible results. Human monocytes produced thromboxane A 2 and prostaglandin E 2 in a typical ratio which ranged from 2.0 to 5.0 (28 experiments). Animal and human sera were similarly effective, while serum obtained from platelet-free blood was much less active. The activity of all sera tested was stable to heating (100°C for 2–10 min) and extreme pH values (pH 2 and 11). It was unstable when the serum was heated at pH 11 and after 2-mercaptoethanol treatment. These observations prompted us to check the effect of polypeptide growth factors having properties similar to those reported above, such as platelet-derived growth factor, fibroblast growth factor, epidermal growth factor as well as insulin and transferrin. None of these, alone or in various combinations, was capable of eliciting a stimulation comparable with that of serum. Stimulation due to sera was, as expected, dose dependently inhibited by acetylsalicylic acid and more efficiently by indomethacin; unexpectedly it was also inhibited by protein synthesis inhibitors such as actinomycin D and cycloheximide in conditions under which no toxic effect of the drugs was evident. On the basis of these results we conclude that: (a) polypeptide growth factor(s) with a molecular weight at least 30000 (as judged by Amicon ultrafiltration) is involved in the regulation of prostaglandin biosynthesis); (b) such a factor(s) acts by inducing rather than by activating the cyclooxygenase system. |
| Databáze: | OpenAIRE |
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