Turnover of extracellular-superoxide dismutase in tissues
Karlsson, K.; Sandström, J.; Edlund, A.; Marklund, S.L.
Laboratory Investigation; A Journal of Technical Methods and Pathology 70(5): 705-710
1994
ISSN/ISBN: 0023-6837 PMID: 8196366 Document Number: 437307
Background: The secretory glycoprotein, extracellular-superoxide dismutase (EC-SOD) is in the body, primarily located to the tissue interstitial space, and in tissue is almost completely composed of homotetrameric high-heparin-affinity C-type. The aim of the present study was to determine the turnover rate of EC-SOD C in tissue and the importance of the heparin-affinity for the retention. Experimental Design: EC-SOD C and two EC-SOD carboxyterminal truncation variants with reduced and absent heparin-affinities, respectively, were labeled with 125I and then subcutaneously and intramuscularly injected into rats. The retentions were followed with repeated determinations with a gamma camera. RESULTS: EC-SOD C displayed a tissue half-life of about 85 hours, whereas the EC-SOD variants with reduced and absent heparin-affinities displayed half-lives of about 20 and 7 hours, respectively. The half-lives were remarkably similar in the intramuscular and subcutaneous injection sites, suggesting rather small overall differences between tissues in EC-SOD C retention. Conclusions: The findings established that EC-SOD C in the tissue interstitium exists almost completely anchored to heparan sulfate proteoglycan via the carboxyterminal heparin-binding domains, and that this binding is the determinant of the long tissue retention of the enzyme. The findings further suggest that reductions in heparin-affinity, e.g., by proteolytic truncation of the highly susceptible heparin-binding domain, may be an important mechanism of elimination of EC-SOD from tissues, both physiologically and as enhanced under pathologic conditions.