Geller D A, Billiar T R
Department of Surgery, University of Pittsburgh, Pennsylvania, USA.
Cancer Metastasis Rev. 1998 Mar;17(1):7-23. doi: 10.1023/a:1005940202801.
Nitric oxide (NO) is a potent biologic mediator with diverse physiologic and pathophysiologic roles. NO is produced from L-arginine by the family of nitric oxide synthase (NOS) enzymes, forming the free radical NO and citrulline as byproduct. Three distinct isoforms of the NOS enzyme have been isolated and represent the products of three different genes. Two of the NOS enzymes are continuously present and are termed constitutive NOS (cNOS). One cNOS enzyme was identified in neurons, and the other in endothelial cells. The two cNOS enzymes are contrasted with the third NOS isoform, inducible NOS, which is not typically expressed in resting cells and must first be induced by certain cytokines, microbial products, or lipopolysaccharide. Since NO production has both beneficial and detrimental consequences, understanding the molecular mechanisms that regulate NOS expression is critical to the control of NO release in homeostatic and pathophysiologic conditions. The purpose of this review is to describe the molecular biology of NO synthases, with particular emphasis on the regulation of the human NO synthase genes. Transcriptional and post-transcriptional regulation of neuronal and endothelial cNOS genes will be reviewed first, followed by the molecular regulation of the inducible NOS gene.
一氧化氮（NO）是一种具有多种生理和病理生理作用的强效生物介质。NO由一氧化氮合酶（NOS）家族的酶从L-精氨酸产生，形成自由基NO和副产物瓜氨酸。已分离出三种不同的NOS酶同工型，它们代表三个不同基因的产物。其中两种NOS酶持续存在，被称为组成型NOS（cNOS）。一种cNOS酶在神经元中被鉴定出来，另一种在内皮细胞中。这两种cNOS酶与第三种NOS同工型——诱导型NOS形成对比，诱导型NOS通常不在静息细胞中表达，必须首先由某些细胞因子、微生物产物或脂多糖诱导。由于NO的产生既有有益的影响也有有害的影响，了解调节NOS表达的分子机制对于在稳态和病理生理条件下控制NO释放至关重要。本综述的目的是描述NO合酶的分子生物学，特别强调人类NO合酶基因的调控。首先将综述神经元和内皮细胞cNOS基因的转录和转录后调控，随后是诱导型NOS基因的分子调控。
