Grupo de Bioquímica dos Oxidantes e Antioxidantes, Centro de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, Lisboa, Portugal.
Antioxid Redox Signal. 2009 Sep;11(9):2223-43. doi: 10.1089/ars.2009.2601.
Hydrogen peroxide (H2O2) has been implicated in the regulation of the transcription factor NF-kappaB, a key regulator of the inflammatory process and adaptive immunity. However, no consensus exists regarding the regulatory role played by H2O2. We discuss how the experimental methodologies used to expose cells to H2O2 produce inconsistent results that are difficult to compare, and how the steady-state titration with H2O2 emerges as an adequate tool to overcome these problems. The redox targets of H2O2 in the NF-kappaB pathway--from the membrane to the post-translational modifications in both NF-kappaB and histones in the nucleus--are described. We also review how H2O2 acts as a specific regulator at the level of the single gene, and briefly discuss the implications of this regulation for human health in the context of kappaB polymorphisms. In conclusion, after near 30 years of research, H2O2 emerges not as an inducer of NF-kappaB, but as an agent able to modulate the activation of the NF-kappaB pathway by other agents. This modulation is generic at the level of the whole pathway but specific at the level of the single gene. Therefore, H2O2 is a fine-tuning regulator of NF-kappaB-dependent processes, as exemplified by its dual regulation of inflammation.
过氧化氢（H2O2）被认为在转录因子 NF-κB 的调节中起作用，NF-κB 是炎症过程和适应性免疫的关键调节因子。然而，关于 H2O2 所起的调节作用尚未达成共识。我们讨论了用于使细胞暴露于 H2O2 的实验方法如何产生难以比较的不一致结果，以及如何通过 H2O2 的稳态滴定来克服这些问题。描述了 H2O2 在 NF-κB 途径中的氧化还原靶标 - 从膜到核内 NF-κB 和组蛋白的翻译后修饰。我们还回顾了 H2O2 如何作为单个基因水平的特定调节剂发挥作用，并简要讨论了在 kappaB 多态性背景下这种调节对人类健康的影响。总之，经过近 30 年的研究，H2O2 并不是 NF-κB 的诱导剂，而是一种能够调节其他因子激活 NF-κB 途径的调节剂。这种调节在整个途径中是通用的，但在单个基因水平上是特异性的。因此，H2O2 是 NF-κB 依赖性过程的精细调节因子，其对炎症的双重调节就是一个例证。
