一氧化氮合酶和环氧合酶途径：细胞信号之间复杂的相互作用

Title:Nitric Oxide Synthase and Cyclooxygenase Pathways: A Complex Interplay in Cellular Signaling

Volume: 23 Issue: 24

Author(s): Andrey Sorokin

Affiliation:

关键词: 环氧合酶、前列腺素、一氧化氮释放信号，非甾体类抗炎药、致癌、NOS系统。

摘要: The cellular reaction to external challenges is a tightly regulated process consisting of integrated processes mediated by a variety of signaling molecules, generated as a result of modulation of corresponding biosynthetic systems. Both, nitric oxide synthase (NOS) and cyclooxygenase (COX) systems, consist of constitutive forms (NOS1, NOS3 and COX-1), which are mostly involved in housekeeping tasks, and inducible forms (NOS2 and COX-2), which shape the cellular response to stress and variety of bioactive agents. The complex interplay between NOS and COX pathways can be observed at least at three levels. Firstly, products of NOS and Cox systems can mediate the regulation and the expression of inducible forms (NOS2 and COX-2) in response of similar and dissimilar stimulus. Secondly, the reciprocal modulation of cyclooxygenase activity by nitric oxide and NOS activity by prostaglandins at the posttranslational level has been shown to occur. Mechanisms by which nitric oxide can modulate prostaglandin synthesis include direct S-nitrosylation of COX and inactivation of prostaglandin I synthase by peroxynitrite, product of superoxide reaction with nitric oxide. Prostaglandins, conversely, can promote an increased association of dynein light chain (DLC) (also known as protein inhibitor of neuronal nitric oxide synthase) with NOS1, thereby reducing its activity. The third level of interplay is provided by intracellular crosstalk of signaling pathways stimulated by products of NOS and COX which contributes significantly to the complexity of cellular signaling. Since modulation of COX and NOS pathways was shown to be principally involved in a variety of pathological conditions, the dissection of their complex relationship is needed for better understanding of possible therapeutic strategies. This review focuses on implications of interplay between NOS and COX for cellular function and signal integration.

Cite this article as:

Andrey Sorokin , Nitric Oxide Synthase and Cyclooxygenase Pathways: A Complex Interplay in Cellular Signaling, Current Medicinal Chemistry 2016; 23 (24) . https://dx.doi.org/10.2174/0929867323666160729105312