1. ATP-Stimulated Degradation of Oxidatively Modified Superoxide Dismutase by Cathepsin D in Cardiac Tissue Extracts
- Author
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Julie M. Fagan, Peter R. Strack, and Lloyd Waxman
- Subjects
Proteases ,Biophysics ,Cathepsin D ,Biochemistry ,Superoxide dismutase ,chemistry.chemical_compound ,Adenosine Triphosphate ,Cathepsin O ,Adenine nucleotide ,Animals ,Protease Inhibitors ,Molecular Biology ,Cathepsin ,biology ,Adenine Nucleotides ,Superoxide Dismutase ,Chemistry ,Myocardium ,Cell Biology ,Hydrogen-Ion Concentration ,Molecular biology ,Kinetics ,Chromatography, Gel ,biology.protein ,Cattle ,Oxidation-Reduction ,Adenosine triphosphate ,Pepstatin - Abstract
Proteins modified by oxidants are rapidly degraded by intracellular proteases. Oxidatively modified superoxide dismutase (Ox-SOD) was degraded 2-8 times faster at both acidic and alkaline pH than the native protein in bovine cardiac tissue extracts. At acidic pH, Ox-SOD hydrolysis was stimulated by ATP and by non-hydrolyzable ATP analogs by up to 50%, but degradation was not stimulated by ATP at alkaline pH. The aspartic protease inhibitor pepstatin completely inhibited the acid Ox-SOD hydrolyzing activity and its stimulation by ATP. This activity eluted from gel filtration with a molecular size of 34-48 kDa and contained the single chain and two mature forms of cathepsin D. Purified cathepsin D degraded Ox-SOD and ATP enhanced the affinity of cathepsin D for oxidatively modified proteins. Thus cardiac tissue proteins modified by oxidants may be substrates for the lysosomal protease cathepsin D.
- Published
- 1996
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