Turnover of extracellular-superoxide dismutase in tissues.
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.


METHODS
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.
Karlsson
K
K
Department of Clinical Chemistry, Umeå University Hospital, Sweden.
Sandström
J
J
Edlund
A
A
Marklund
S L
SL
D000818:Animals; D001345:Autoradiography; D002846:Chromatography, Affinity; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D006207:Half-Life; D006801:Humans; D007273:Injections, Intramuscular; D007279:Injections, Subcutaneous; D007457:Iodine Radioisotopes; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism / Q000493:pharmacokinetics; D013482:Superoxide Dismutase / Q000302:isolation & purification / Q000378:metabolism* / Q000493:pharmacokinetics; D013997:Time Factors; D014018:Tissue Distribution
D007457:Iodine Radioisotopes; D011994:Recombinant Proteins; D013482:Superoxide Dismutase