Staal F J, Roederer M, Herzenberg L A, Herzenberg L A
Department of Genetics, Stanford University School of Medicine, CA 94305.
Proc Natl Acad Sci U S A. 1990 Dec;87(24):9943-7. doi: 10.1073/pnas.87.24.9943.
The activation of nuclear factor kappa B (NF-kappa B) has been implicated in the regulation of transcription of a variety of genes and has been shown to be essential for the expression of genes controlled by the long terminal repeat of human immunodeficiency virus (HIV LTR). We show here that intracellular thiol levels play a key role in regulating this process. That is, stimulation with tumor necrosis factor alpha and/or phorbol 12-myristate 13-acetate activates NF-kappa B and markedly decreases intracellular thiols; N-acetyl-L-cysteine, an efficient thiol source, prevents this thiol decrease and blocks the activation of NF-kappa B; and the lack of activated NF-kappa B prevents the activation of the HIV LTR and the transcription of genes under its control. These findings reveal a previously unrecognized genetic regulatory mechanism in which cytokine-induced shifts in intracellular thiol levels are crucial in the control of NF-kappa B activity and thereby influence the spectrum of genes expressed by cytokine-stimulated cells.
核因子κB（NF-κB）的激活与多种基因的转录调控有关，并且已证明对受人类免疫缺陷病毒长末端重复序列（HIV LTR）控制的基因表达至关重要。我们在此表明，细胞内硫醇水平在调节这一过程中起关键作用。也就是说，用肿瘤坏死因子α和/或佛波醇12-肉豆蔻酸酯13-乙酸酯刺激可激活NF-κB并显著降低细胞内硫醇水平；N-乙酰-L-半胱氨酸作为一种有效的硫醇来源，可防止这种硫醇水平降低并阻断NF-κB的激活；而缺乏活化的NF-κB则会阻止HIV LTR的激活及其控制下的基因转录。这些发现揭示了一种以前未被认识的基因调控机制，其中细胞因子诱导的细胞内硫醇水平变化在控制NF-κB活性方面至关重要，从而影响细胞因子刺激的细胞所表达的基因谱。
