Kröncke K D, Suschek C V, Kolb-Bachofen V
Research Group Immunobiology in the Biomedical Research Centre, Heinrich-Heine-University, Düsseldorf, Germany.
Antioxid Redox Signal. 2000 Fall;2(3):585-605. doi: 10.1089/15230860050192341.
We summarize here our current knowledge about inducible nitric oxide synthase (NOS) activity in human diseases and disorders. As basic research discovers more and more effects of low or high concentrations of NO toward molecular and cellular targets, successful therapies involving inhibition of NO synthesis or application of NO to treat human diseases are still lacking. This is in part due to the fact that the impact of NO on cell function or death are complex and often even appear to be contradictory. NO may be cytotoxic but may also protect cells from a toxic insult; it is apoptosis-inducing but also exhibits prominent anti-apoptotic activity. NO is an antioxidant but may also compromise the cellular redox state via oxidation of thiols like glutathione. NO may activate specific signal transduction pathways but is also reported to inhibit exactly these, and NO may activate or inhibit gene transcription. The situation may even be more complicated, because NO, depending on its concentration, may react with oxygen or the superoxide anion radical to yield reactive species with a much broader chemical reaction spectrum than NO itself. Thus, the action of NO during inflammatory reactions has to be considered in the context of timing and duration of its synthesis as well as stages and specific events in inflammation.
在此，我们总结目前关于诱导型一氧化氮合酶（NOS）活性在人类疾病和病症中的知识。随着基础研究发现低浓度或高浓度的一氧化氮对分子和细胞靶点的影响越来越多，仍然缺乏涉及抑制一氧化氮合成或应用一氧化氮来治疗人类疾病的成功疗法。部分原因在于一氧化氮对细胞功能或死亡的影响很复杂，甚至常常看似相互矛盾。一氧化氮可能具有细胞毒性，但也可能保护细胞免受毒性损伤；它可诱导细胞凋亡，但也表现出显著的抗凋亡活性。一氧化氮是一种抗氧化剂，但也可能通过氧化谷胱甘肽等硫醇而损害细胞的氧化还原状态。一氧化氮可能激活特定的信号转导途径，但也有报道称它恰恰会抑制这些途径，并且一氧化氮可能激活或抑制基因转录。情况甚至可能更复杂，因为一氧化氮根据其浓度不同，可能与氧气或超氧阴离子自由基反应，生成比一氧化氮本身具有更广泛化学反应谱的活性物质。因此，在炎症反应过程中一氧化氮的作用必须结合其合成的时间和持续时间以及炎症的阶段和特定事件来考虑。
