一氧化氮和过氧亚硝酸盐所致DNA损伤的化学机制

The chemistry of DNA damage from nitric oxide and peroxynitrite.

作者信息

Burney S, Caulfield J L, Niles J C, Wishnok J S, Tannenbaum S R

机构信息

Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

出版信息

Mutat Res. 1999 Mar 8;424(1-2):37-49. doi: 10.1016/s0027-5107(99)00006-8.

DOI:10.1016/s0027-5107(99)00006-8

PMID:10064848

Abstract

Nitric oxide is a key participant in many physiological pathways; however, its reactivity gives it the potential to cause considerable damage to cells and tissues in its vicinity. Nitric oxide can react with DNA via multiple pathways. Once produced, subsequent conversion of nitric oxide to nitrous anhydride and/or peroxynitrite can lead to the nitrosative deamination of DNA bases such as guanine and cytosine. Complex oxidation chemistry can also occur causing DNA base and sugar oxidative modifications. This review describes the different mechanisms by which nitric oxide can damage DNA. First, the physiological significance of nitric oxide is discussed. Details of nitric oxide and peroxynitrite chemistry are then given. The final two sections outline the mechanisms underlying DNA damage induced by nitric oxide and peroxynitrite.

摘要

一氧化氮是许多生理途径中的关键参与者；然而，其反应活性使其有可能对周围的细胞和组织造成相当大的损害。一氧化氮可通过多种途径与DNA发生反应。一氧化氮一旦产生，随后转化为亚硝酸酐和/或过氧亚硝酸盐会导致鸟嘌呤和胞嘧啶等DNA碱基的亚硝化脱氨。还会发生复杂的氧化化学反应，导致DNA碱基和糖的氧化修饰。本综述描述了一氧化氮损害DNA的不同机制。首先，讨论了一氧化氮的生理意义。然后给出了一氧化氮和过氧亚硝酸盐化学的详细信息。最后两节概述了一氧化氮和过氧亚硝酸盐诱导DNA损伤的潜在机制。