Effect of neurotoxic metal ions on the proteolytic activities of the 20S proteasome from bovine brain
Effect of neurotoxic metal ions on the proteolytic activities of the 20S proteasome from bovine brain
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DOI：
10.1007/s00775-002-0352-4
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发表时间：
2002-09-01
影响因子：
3
通讯作者：
Eleuteri, AM
中科院分区：
文献类型：
--
作者：
Amici, M;Forti, K;Eleuteri, AM
研究了神经毒性金属离子诱导的氧化应激对脑20S蛋白酶体或多催化蛋白酶复合体(MPC)性质的影响。增加Fe(III)、Fe(II)、Cu(II)或Zn(II)对20S蛋白酶体的主要水解酶活性：类胰蛋白酶(T-L)、类糜蛋白酶(CHT-L)、肽基谷氨酰胺水解酶(PGPH)、支链氨基酸偏好(BrAAP)和酪蛋白水解酶活性有影响，但作用方式不同。T-L活性被两种铁离子逐渐激活，而被铜、锌离子抑制。除锌离子外，所有受试金属盐对CHT-L和PGPH活性均有抑制作用，而对BrAAP活性有广泛的激活作用。此外，亚铁盐还增加了酪蛋白的降解率。这些功能效应似乎与氧化诱导的修饰有关，暴露于金属离子后，羰基增加证明了这一点。此外，用抗X、抗Y和抗Z抗体进行的蛋白质印迹分析也支持亚铁盐对催化亚基的修饰。这些结果清楚地表明，金属催化氧化强烈影响大脑20S蛋白酶体的功能，尽管催化亚基似乎受到氧化现象的不同影响。
The effect of oxidative stress induced by neurotoxic metal ions on the properties of the brain 20S proteasome or multicatalytic proteinase complex (MPC) has been studied. Exposure of the 20S proteasome to increasing amounts of Fe(III), Fe(II), Cu(II) or Zn(II) affects its main hydrolytic activities: trypsin-like (T-L), chymotrypsin-like (ChT-L), peptidylglutamyl-peptide hydrolase (PGPH), branched-chain amino acid preferring (BrAAP) and caseinolytic activities, although in different ways. T-L activity showed gradual activation by both iron ions but inhibition by Cu(II) and Zn(II). ChT-L and PGPH activities were inhibited whereas BrAAP activity was widely activated by all the tested metal salts except for zinc ions. Moreover, the exposure to ferrous salt increased the degradation rate of casein. The functional effects appear to be linked to oxidation-induced modifications, as demonstrated by an increase of carbonyl groups following the exposure to metal ions. In addition, modifications induced by ferrous salt on the catalytic subunits were also supported by western blot analyses performed using anti-X, anti-Y and anti-Z antibodies. The results obtained clearly indicate that metal-catalyzed oxidation strongly affects the functions of the brain 20S proteasome, even though the catalytic subunits seem to be differently influenced by oxidative phenomena.