Kim P K, Zamora R, Petrosko P, Billiar T R
Department of Surgery Laboratories, University of Pittsburgh School of Medicine, PA 15213, USA.
Int Immunopharmacol. 2001 Aug;1(8):1421-41. doi: 10.1016/s1567-5769(01)00088-1.
Nitric oxide (NO) is a multi-faceted molecule with dichotomous regulatory roles in many areas of biology. The complexity of its biological effects is a consequence of its numerous potential interactions with other molecules such as reactive oxygen species (ROS), metal ions, and proteins. The effects of NO are modulated by both direct and indirect interactions that can be dose-dependent and cell-type specific. For example, in some cell types NO can promote apoptosis, whereas in other cells NO inhibits apoptosis. In hepatocytes, NO can inhibit the main mediators of cell death-caspase proteases. Moreover, low physiological concentrations of NO can inhibit apoptosis, but higher concentrations of NO may be toxic. High NO concentrations lead to the formation of toxic reaction products like dinitrogen trioxide or peroxynitrite that induce cell death, if not by apoptosis, then by necrosis. Long-term exposure to nitric oxide in certain conditions like chronic inflammatory states may predispose cells to tumorigenesis through DNA damage, inhibition of DNA repair, alteration in programmed cell death, or activation of proliferative signaling pathways. Understanding the regulatory mechanisms of NO in apoptosis and carcinogenesis will provide important clues to the diagnosis and treatment of tissue damage and cancer. In this article we have reviewed recent discoveries in the regulatory role of NO in specific cell types, mechanisms of pro-apoptotic and anti-apoptotic induction by NO, and insights into the effects of NO on tumor biology.
一氧化氮（NO）是一种具有多面性的分子，在许多生物学领域发挥着二元调节作用。其生物学效应的复杂性源于它与其他分子（如活性氧（ROS）、金属离子和蛋白质）的众多潜在相互作用。NO的效应通过直接和间接相互作用进行调节，这些相互作用可能具有剂量依赖性和细胞类型特异性。例如，在某些细胞类型中，NO可促进细胞凋亡，而在其他细胞中，NO则抑制细胞凋亡。在肝细胞中，NO可抑制细胞死亡的主要介质——半胱天冬酶蛋白酶。此外，生理浓度较低的NO可抑制细胞凋亡，但较高浓度的NO可能具有毒性。高浓度的NO会导致有毒反应产物的形成，如三氧化二氮或过氧亚硝酸盐，这些产物可诱导细胞死亡，若不是通过凋亡，就是通过坏死。在某些条件下，如慢性炎症状态下长期暴露于一氧化氮，可能会通过DNA损伤、抑制DNA修复、改变程序性细胞死亡或激活增殖信号通路，使细胞易发生肿瘤igenesis。了解NO在细胞凋亡和肿瘤发生中的调节机制，将为组织损伤和癌症的诊断与治疗提供重要线索。在本文中，我们综述了NO在特定细胞类型中的调节作用、NO诱导促凋亡和抗凋亡的机制以及NO对肿瘤生物学影响的最新发现。
