Pharmacokinetics of extracellular-superoxide dismutase in the vascular system☆
| Autor: | Jan Sandström, Kurt Karlsson, Thomas Edlund, Anders Edlund, Stefan L. Marklund |
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| Rok vydání: | 1993 |
| Předmět: |
Male
Free Radicals Kidney Biochemistry law.invention Superoxide dismutase chemistry.chemical_compound Ischemia Superoxides law Physiology (medical) medicine Animals chemistry.chemical_classification Lagomorpha biology Heparin Superoxide Dismutase Chemistry Genetic Variation Heparan sulfate biology.organism_classification Recombinant Proteins Kinetics Enzyme medicine.anatomical_structure Reperfusion biology.protein Recombinant DNA Biophysics Blood Vessels Female Dismutase Rabbits medicine.drug |
| Zdroj: | Free Radical Biology and Medicine. 14:185-190 |
| ISSN: | 0891-5849 |
| DOI: | 10.1016/0891-5849(93)90009-j |
| Popis: | Extracellular-superoxide dismutase C (EC-SOD C) is a secretory tetrameric Cu- and Zn-containing glycoprotein which has high affinity for heparin and heparan sulfate. Upon intravenous injection into rabbits, recombinant human (rh) EC-SOD C was found to be rapidly 97-98% sequestered to the vascular wall, forming an equilibrium with the plasma phase. Recombinant EC-SOD truncation variants with reduced, T216, and without, T213, heparin affinity were found to be sequestered to a reduced extent and not at all, respectively, establishing the importance of the heparin affinity for this behaviour. The halflife of rhEC-SOD C in the vasculature was of the order of 20 h. Injection of large doses resulted in saturation of the binding of rhEC-SOD C to the vascular wall. Scatchard analysis revealed a heterogeneity in affinity of the ligands on the vascular wall. The maximal binding capacity was very high. The equilibration of rhEC-SOD C to the vascular wall of an organ, clamped during enzyme injection, and the primary equilibration phase was studied by comparing binding to a clamped and reperfused kidney with binding to the contralateral control kidney. rhEC-SOD C injected in a low dose was found to equilibrate very slowly to the reperfused kidney with a halftime of about 2 h. With higher rhEC-SOD C doses, at which evidence for saturation is seen, and with the variant rhEC-SOD with reduced heparin affinity. T216, very rapid equilibrations were found.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Databáze: | OpenAIRE |
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