Inhibition of proteasome activity by selected amino acids
Inhibition of proteasome activity by selected amino acids
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DOI：
10.1016/s0026-0495(03)00094-5
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发表时间：
2003-07-01
影响因子：
9.8
通讯作者：
Duckworth, WC
中科院分区：
文献类型：
--
作者：
Hamel, FG;Upward, JL;Duckworth, WC
细胞蛋白质稳态是合成和降解之间的平衡。蛋白质的降解受激素（胰岛素）和营养素（氨基酸）的调节。某些氨基酸能够减少细胞蛋白质降解，有证据表明这是通过改变溶酶体功能介导的。然而，蛋白酶体，主要的胞质蛋白质降解机制，被证明在控制细胞中的蛋白质周转中发挥核心作用。在这项研究中，我们表明，氨基酸，异亮氨酸，亮氨酸，酪氨酸，苯丙氨酸，色氨酸，赖氨酸和精氨酸能够抑制胰凝乳蛋白酶样活性的蛋白酶体的剂量依赖性的方式。亮氨酸、酪氨酸和苯丙氨酸在正常血清浓度下具有实质性影响。与来自肝脏的类似制剂相比，来自肌肉的蛋白酶体制剂的效果更大。假设氨基酸诱导的细胞蛋白质降解的变化反映了蛋白酶体活性的抑制变化，我们可以得出结论，氨基酸控制细胞蛋白质降解介导的，至少部分，通过蛋白酶体。(C)2003年爱思唯尔公司All rights reserved.
Cellular protein homeostasis is a balance between synthesis and degradation. Protein degradation is regulated by hormones leg, insulin) and nutrients leg, amino acids). Certain amino acids are capable of decreasing cellular protein degradation, with evidence that this is mediated through altered lysosomal function. However, proteasomes, the major cytosolic protein degrading machinery, are being shown to play a central role in the control of protein turnover in the cell. In this study we show that the amino acids, isoleucine, leucine, tyrosine, phenylalanine, tryptophan, lysine, and arginine are capable of inhibiting the chymotrypsin-like activity of the proteasome in a dose-dependent manner. Leucine, tyrosine, and phenylalanine have a substantial effect at normal serum concentrations. The effect was greater in a proteasome preparation derived from muscle compared to a similar preparation from liver. On the assumption that amino acid-induced alterations in cellular protein degradation reflect the inhibitory changes in proteasomal activity shown here, we may conclude that amino acid control of cellular protein degradation is mediated, at least in part, through proteasomes. (C) 2003 Elsevier Inc. All rights reserved.