Thioredoxin is required for S-nitrosation of procaspase-3 and the inhibition of apoptosis in Jurkat cells
Thioredoxin is required for S-nitrosation of procaspase-3 and the inhibition of apoptosis in Jurkat cells
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DOI：
10.1073/pnas.0704898104
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发表时间：
2007-07-10
影响因子：
11.1
通讯作者：
Marletta, Michael A.
中科院分区：
文献类型：
--
作者：
Mitchell, Douglas A.;Morton, Sarah U.;Marletta, Michael A.
S亚硝化是蛋白质半胱氨酸残基上NO的翻译后氧化加成反应，被认为是一种不依赖于cGMP的信号通路[Hess DT，MatSumoto A，Kim So，Matt HE，Stamler JS(2005)NAT Rev Mol Cell Biol 6：150-166]。S亚硝化的一个悖论是，尽管NO与硫醇具有混杂反应活性，但体内只有一小部分反应性半胱氨酸被修饰，排除了游离NO反应作为S亚硝化的主要机制。在这里，我们发现在培养的人T细胞中，原天冬氨酸氨基转移酶-3和硫氧还蛋白-1(TRX)之间发生了一种特异性的转亚硝化反应，从而阻止了细胞的凋亡。Trx参与催化细胞内的转亚硝化反应可能是普遍的，因为这种蛋白质具有大量的蛋白质-蛋白质相互作用，并在细胞氧化还原平衡[Powis G，Montfort WR(2001)Annu Rev Pharmacol Toxicol 41：261295]，细胞中的亚硝硫醇含量[Haendeler J，Hoffmann J，Tischler V，Berk BC，Zeiher AM，Dimmerer S(2002)NAT Cell Biol 4：743-749]以及抗凋亡信号中发挥关键作用。
S-nitrosation is a posttranslational, oxidative addition of NO to cysteine residues of proteins that has been proposed as a cGMP-independent signaling pathway [Hess DT, Matsumoto A, Kim SO, Marshall HE, Stamler JS (2005) Nat Rev Mol Cell Biol 6:150-166]. A paradox of S-nitrosation is that only a small set of reactive cysteines are modified in vivo despite the promiscuous reactivity NO exhibits with thiols, precluding the reaction of free NO as the primary mechanism of S-nitrosation. Here we show that a specific transnitrosation reaction between procaspase-3 and thioredoxin-1 (Trx) occurs in cultured human T cells and prevents apoptosis. Trx participation in catalyzing transnitrosation reactions in cells may be general because this protein has numerous protein-protein interactions and plays a key role in cellular redox homeostasis [Powis G, Montfort WR (2001) Annu Rev Pharmacol Toxicol 41:261295], nitrosothiol content in cells [Haendeler J, Hoffmann J, Tischler V, Berk BC, Zeiher AM, Dimmeler S (2002) Nat Cell Biol 4:743-749], and antiapoptotic signaling.