Trehalose accumulation during cellular stress protects cells and cellular proteins from damage by oxygen radicals
Trehalose accumulation during cellular stress protects cells and cellular proteins from damage by oxygen radicals
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DOI：
10.1074/jbc.m101487200
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发表时间：
2001-06-29
影响因子：
4.8
通讯作者：
Goldberg, AL
中科院分区：
文献类型：
--
作者：
Benaroudj, N;Lee, DH;Goldberg, AL
在许多生物体中，二糖海藻糖在热激和稳定期显著积累，增强耐热性并减少变性蛋白质的聚集。在这里，我们报告了海藻糖在保护细胞免受氧自由基侵害中的新作用。将酿酒酵母暴露于温和的热休克（38 degreesC）或蛋白酶体抑制剂（MG 132）诱导海藻糖积累，并显著增加细胞暴露于自由基生成系统（H2 O2/铁）后的活力。当细胞恢复到正常生长温度（28 ℃）或从培养基中除去MG 132时，海藻糖含量和对氧自由基的抗性迅速下降，并且不能合成海藻糖的突变体比野生型细胞对氧自由基的杀伤更敏感。外源提供海藻糖增强了突变体细胞对H2 O2的抗性。细胞暴露于H2 O2引起细胞蛋白质中氨基酸的氧化损伤，海藻糖积累被发现可以减少这种损伤。即使短暂暴露于H2 O2后，海藻糖缺陷突变体表现出比野生型细胞更高的氧化损伤蛋白质含量。海藻糖的积累减少了受损蛋白的初始外观，可能是作为一种自由基清除剂。因此，海藻糖在应激细胞中的积累在保护细胞成分免受氧化损伤方面起着重要作用。
The disaccharide trehalose, which accumulates dramatically during heat shock and stationary phase in many organisms, enhances thermotolerance and reduces aggregation of denatured proteins. Here we re port a new role for trehalose in protecting cells against oxygen radicals. Exposure of Saccharomyces cerevisiae to a mild heat shock (38 degreesC) or to a proteasome inhibitor (MG132) induced trehalose accumulation and markedly increased the viability of the cells upon exposure to a free radical-generating system (H2O2/iron). When cells were returned to normal growth temperature (28 degreesC) or MG132 was removed from the medium, the trehalose content and resistance to oxygen radicals decreased rapidly, Furthermore, a mutant unable to synthesize trehalose was much more sensitive to killing by oxygen radicals than wild-type cells. Providing trehalose exogenously enhanced the resistance of mutant cells to H2O2. Exposure of cells to H2O2 caused oxidative damage to amino acids in cellular proteins, and trehalose accumulation was found to reduce such damage. After even brief exposure to H2O2, the trehalose-deficient mutant exhibited a much higher content of oxidatively damaged proteins than wild-type cells. Trehalose accumulation decreased the initial appearance of damaged proteins, presumably by acting as a free radical scavenger. Therefore, trehalose accumulation in stressed cells plays a major role in protecting cellular constituents from oxidative damage.