ATP-stimulated degradation of oxidatively modified superoxide dismutase by cathepsin D in cardiac tissue extracts.
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.
Strack
P R
PR
Department of Animal Sciences, Rutgers University, New Brunswick, New Jersey 08903-0231, USA.
Waxman
L
L
Fagan
J M
JM
D000227:Adenine Nucleotides / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002402:Cathepsin D / Q000302:isolation & purification / Q000378:metabolism*; D002417:Cattle; D002850:Chromatography, Gel; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D009206:Myocardium / Q000201:enzymology*; D010084:Oxidation-Reduction; D011480:Protease Inhibitors / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism*
D000227:Adenine Nucleotides; D011480:Protease Inhibitors; D000255:Adenosine Triphosphate; D013482:Superoxide Dismutase; D002402:Cathepsin D