Low levels of inorganic lead noncompetitively inhibit μ-calpain

被引:4
作者
Audesirk, T [1 ]
Pedersen, C [1 ]
Audesirk, G [1 ]
Kern, M [1 ]
机构
[1] Univ Colorado, Dept Biol, Denver, CO 80217 USA
关键词
lead; Pb2+; calpain; calcium;
D O I
10.1016/S0300-483X(98)00127-9
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Calpain is a ubiquitous calcium-dependent cysteine protease, whose cytoskeletal protein substrates suggest that it may be important in neuronal differentiation. Lead (Pb2+) is known to substitute for Ca2+ in a variety of intracellular processes, and interferes with the development of hippocampal neurons in vitro. We found that free Pb2+ at 1 nM does not activate calpain in the absence of Ca2+. Pb2+ inhibited the activity of calpain; the degree of calpain inhibition was dependent on an interaction between concentrations of both Ca2+ and Pb2+. In the presence of 1 mu M free Ca2+, 10 pM free Pb2+ reduced calpain activity, but in the presence of 100 mu M free Ca2+ I nM free Pb2+ failed to inhibit calpain. This provides evidence that Pb2+ competes for the Ca2+ binding sites on calpain. In the presence of 40 mu M free Ca2+, 1 nM free Pb2+ significantly reduces V-max without altering K-m, suggesting that Pb2+ acts as a noncompetitive inhibitor of calpain. Inhibition of calpain is one mechanism by which Pb2+ may interfere with neuronal development. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.
引用
收藏
页码:169 / 174
页数:6
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