Details

Autor(en) / Beteiligte

• Adachi, Tetsuo
• Morihara, Naoaki
• Yamazaki, Naoya
• Yamada, Harutaka
• Futenina, Arao
• Kato, Katsumi
• Hirano, Kazuyuki

Titel

An Arginine-213 to Glycine Mutation in Human Extracellular-Superoxide Dismutase Reduces Susceptibility to Trypsin-Like Proteinases

Ist Teil von

• Journal of biochemistry (Tokyo), 1996-07, Vol.120 (1), p.184-188

Ort / Verlag

England: Oxford University Press

Erscheinungsjahr

1996

Quelle

MEDLINE

Beschreibungen/Notizen

• Molecular genetic studies of extracellular-superoxide dismutase (EC-SOD) have shown that individuals with high serum EC-SOD content have a single base substitution generating the exchange of glycine for arginine-213 (R213G) in the heparin-binding domain of this enzyme [Sandström J. et al. (1994) J. Biol. Chem. 269, 19163-19166], which causes the impairment of its binding ability to endothelial cell surface [Adachi T. et al. (1996) Biochem. J. 313, 235-239]. Serum EC-SOD in healthy individuals without the above mutation is heterogeneous with regard to heparin affinity and consists of five fractions, forms (I) to (V), of which (IV) and (V) are the main fractions with high affinity for heparin [AdaChi T. et al. (1995) J. Biochem. 117, 586-590], whereas the major fraction in hemodialysis patients was serum EC-SOD form (I), which is thought to be the proteolytic truncated form. On the other hand, serum EC-SOD in both healthy individuals and hemodialysis patients with the R213G mutation consisted mainly of the high heparin-affinity type. This observation suggests that the susceptibility of EC-SOD to protelnases is reduced by the R213G mutation. The affinity of normal EC-SOD (n-EC-SOD) for heparin decreased by the treatment with trypsin, accompanied by a reduction in the molecular mass. The IC50 of trypsin for the heparin affinity of R213G mutant EC-SOD (m-EC-SOD) was 0.15 μg/ml, fivefold that for n-EC-SOD. Heparin affinity of n-EC-SOD was again more susceptible to neutrophils than that of m-EC-SOD. These results suggested that m-EC-SOD is more resistant to trypsin and neutrophil-release trypsin-like protelnases than n-EC SOD, which causes the heparin affinity of serum EC-SOD to differ in individuals with and without the R213G mutation.