ATP-stimulated degradation of oxidatively modified superoxide dismutase by cathepsin D in cardiac tissue extracts

Biochemical and Biophysical Research Communications
P R StrackJ M Fagan

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.

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