López-Farré A, Rodríguez-Feo J A, Sánchez de Miguel L, Rico L, Casado S
Nephrology, Hypertension and Cardiovascular Research Laboratory, Fundacion Jimeniz Diaz, Madrid, Spain.
Int J Biochem Cell Biol. 1998 Oct;30(10):1095-106. doi: 10.1016/s1357-2725(98)00071-5.
Cell death occurs by either apoptosis or necrosis. Apoptosis is a cellular event in which a sequence of biochemical and morphological changes conclude in the death of the cell. Apoptosis is an important mechanism to control the number of cells and maintain tissue architecture. Nitric oxide (NO) is a multifunctional molecule that is synthesized by a family of enzymes, namely nitric oxide synthases (NOS). NO is implicated in several physiological functions within the microvascular environment, i.e. regulation of vascular tone, antiplatelet and antileukocyte properties and modulation of cell growth. Several investigations have demonstrated effects of NO on gene transcription. In this regard, NO has been also implicated in the apoptotic processes. The goal of the present review is to summarize the current knowledge about the relationship between NO and different genes involved in the apoptotic phenomena with focus in the cells of the microvascular environment, i.e. monocytes/macrophages, endothelium and vascular smooth muscle cells. Different studies have revealed that stimulation and inhibition of different genes are required to stimulate apoptosis. NO modulates the expression of bcl-2 family members, p53, interleukin-1 beta-converting enzyme family proteases and the cytokine receptor Fas. Therefore, NO generated from NO donors or synthesized by NOS induces cell death via apoptosis in a variety of different cell types. On the other hand, in the endothelial cells NO seems to have a relevant role in the maintenance of the confluent endothelial monolayer inhibiting apoptotic-related mechanisms. Furthermore, the redox states of the cells play an important role in the effects of NO as promotor of apoptosis. There have been exciting advances in the understanding of the molecular relationship between apoptosis and NO. Therefore, NO could be an important mediator to consider in the context of future therapeutic applications particularly considering apoptosis as a mechanism to maintain vascular architecture.
细胞死亡通过凋亡或坏死发生。凋亡是一种细胞事件，其中一系列生化和形态学变化最终导致细胞死亡。凋亡是控制细胞数量和维持组织结构的重要机制。一氧化氮（NO）是一种多功能分子，由一族酶即一氧化氮合酶（NOS）合成。NO参与微血管环境中的多种生理功能，即血管张力调节、抗血小板和抗白细胞特性以及细胞生长调节。多项研究已证明NO对基因转录的影响。在这方面，NO也与凋亡过程有关。本综述的目的是总结关于NO与参与凋亡现象的不同基因之间关系的当前知识，重点关注微血管环境中的细胞，即单核细胞/巨噬细胞、内皮细胞和血管平滑肌细胞。不同研究表明，刺激和抑制不同基因对于诱导凋亡是必需的。NO调节bcl-2家族成员、p53、白细胞介素-1β转换酶家族蛋白酶和细胞因子受体Fas的表达。因此，由NO供体产生或由NOS合成的NO通过凋亡在多种不同细胞类型中诱导细胞死亡。另一方面，在内皮细胞中，NO似乎在维持汇合的内皮单层、抑制凋亡相关机制方面具有重要作用。此外，细胞的氧化还原状态在NO作为凋亡促进剂的作用中起重要作用。在理解凋亡与NO之间的分子关系方面已经取得了令人兴奋的进展。因此，NO可能是未来治疗应用中需要考虑的重要介质，特别是将凋亡视为维持血管结构的机制时。
