Isolation and characterization of coenzyme A glutathione disulfide as a parathyroid-derived vasoconstrictive factor
| Autor: | Hartmut Schlüter, Walter Zidek, Nina Stephan, Martin Tepel, Joachim Jankowski, Markus van der Giet, Jiankai Luo, Anna Schröter |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
medicine.medical_specialty
Vascular smooth muscle Coenzyme A Acetates Rats Inbred WKY Muscle Smooth Vascular Parathyroid Glands chemistry.chemical_compound Physiology (medical) Internal medicine medicine Purinergic P2 Receptor Antagonists Animals Humans Vasoconstrictor Agents Disulfides Pyridoxal phosphate Cells Cultured Chromatography High Pressure Liquid Mercaptoethanol Dose-Response Relationship Drug business.industry Angiotensin II Glutathione Chromatography Ion Exchange Rats Molecular Weight Dose–response relationship Endocrinology chemistry Purinergic P1 Receptor Antagonists Pyridoxal Phosphate Spectrometry Mass Matrix-Assisted Laser Desorption-Ionization Glutathione disulfide Theobromine Cardiology and Cardiovascular Medicine Thymidine business Cell Division |
| Zdroj: | Circulation. 102(20) |
| ISSN: | 1524-4539 |
| Popis: | Background —Coenzyme A glutathione disulfide (CoA-SSG) was recently isolated from bovine adrenal glands and was shown to be a renal vasoconstrictor. The identification of CoA-SSG in human parathyroid glands and its action on cultured vascular smooth muscle cells (VSMCs) are described here. Methods and Results —After purification to homogeneity by several chromatographic steps, CoA-SSG was identified by matrix-assisted laser desorption/ionization mass spectrometry and enzymatic analysis. The dose-dependent growth-stimulating effect of CoA-SSG on VSMCs, measured by the [ 3 H]thymidine method, is characterized by a threshold of 10 − 8 mol/L and a maximum effect of 10 μmol/L, increasing VSMC proliferation 254±21% above control. A dose of 10 μmol/L methylmalonyl-CoA and 10 μmol/L CoA increased the rate of proliferation of VSMCs only by 178±43% and 50±42% above control, respectively. Glutathione has no proliferative effect on VSMCs. The growth-stimulating effect of CoA-SSG (1 μmol/L) was decreased by the antagonists 3,7-dimethyl-1-propargylxanthine (DMPX; 11 μmol/L) (38% compared with CoA-SSG without antagonist) and pyridoxal-phosphate-6-azophenyl-2,4-disulfonic acid (PPADS; 10 μmol/L) (48% compared with CoA-SSG without antagonist; each P 2 and partly via P 2 Y 1 and/or P 2 Y 4 receptor. Conclusions —CoA-SSG may play a regulatory role in VSMC growth as a progression factor and thereby could play an important role in development of hypertension. |
| Databáze: | OpenAIRE |
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