The tetrameric extracellular superoxide dismutase (EC-SOD) in human tissues and plasma has previously been found to be heterogenous with regard to heparin affinity and could be divided into at least three classes: A, lacking heparin affinity; B, with weak affinity; and C, with strong affinity. Using rigorous extraction conditions and an extensive set of anti-proteolytic agents, tissue EC-SOD is now shown to be almost exclusively of native homotetrameric C-class. Plasma EC-SOD on the other hand is shown to be mainly composed of a complex mixture of heterotetramers with modifications probably residing in the C-terminal heparin-binding domain. Proteolytic truncations appear to be a major cause of this heterogeneity. The findings suggest that, since 99% of the EC-SOD in the human body exists in the extravascular space of tissue, EC-SOD is primarily synthesized in tissues and secreted as homotetrameric native EC-SOD C. This tissue EC-SOD C should exist almost completely sequestered by heparin sulphate proteoglycans. C-terminal modifications subsequently occurring in the EC-SOD C would weaken the binding to heparan sulphate proteoglycan, facilitate entrance to the vasculature through capillaries and lymph flow, and finally result in the heterogeneous plasma EC-SOD pattern. With the new extraction and analysis procedure, the tissue content of EC-SOD is found to be higher than previously reported. It is found, for example, when compared with Mn-SOD, to be higher in umbilical cord and uterus, about equal in placenta and testis and as high as that of CuZn-SOD in umbilical cord. The findings suggest that the protection level against superoxide radicals provided by EC-SOD in the tissue interstitial space, given the small distribution volume, is not much less prominent than that bestowed on the intracellular space by CuZn-SOD and Mn-SOD.
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Research Article|
September 15 1993
Heparin-affinity patterns and composition of extracellular superoxide dismutase in human plasma and tissues
J Sandström;
J Sandström
*Department of Microbiology, University of Umeå S-901 87 Umeå, Sweden
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K Karlsson;
K Karlsson
†Deparment of Clinical Chemistry, Umeå University Hospital, S-901 85 Umeå, Sweden
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T Edlund;
T Edlund
*Department of Microbiology, University of Umeå S-901 87 Umeå, Sweden
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S L Marklund
S L Marklund
†Deparment of Clinical Chemistry, Umeå University Hospital, S-901 85 Umeå, Sweden
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Publisher: Portland Press Ltd
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 1993 The Biochemical Society, London
1993
Biochem J (1993) 294 (3): 853–857.
Citation
J Sandström, K Karlsson, T Edlund, S L Marklund; Heparin-affinity patterns and composition of extracellular superoxide dismutase in human plasma and tissues. Biochem J 15 September 1993; 294 (3): 853–857. doi: https://doi.org/10.1042/bj2940853
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