对一氧化氮的转录反应是广泛存在且依赖于来源的。

Transcriptional responses to nitric oxide are widescale and source-dependent.

作者信息

Schindler Joseph C, Seth Puneet, Premont Richard T, Stamler Jonathan S

机构信息

Institute for Transformative Molecular Medicine, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA; Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.

Institute for Transformative Molecular Medicine, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA; Harrington Discovery Institute, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA.

出版信息

J Biol Chem. 2025 Jul 11;301(8):110476. doi: 10.1016/j.jbc.2025.110476.

DOI:10.1016/j.jbc.2025.110476

PMID:40653200

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12355106/

Abstract

The transcriptomic effects of nitric oxide (NO) have been widely studied across phylogeny. However, while gene expression is canonically altered by NO, general principles have not emerged. Here, we characterize genetic regulation within a single cell type after exposure to NO derived from endogenous or synthetic donor compounds or produced by 3 different NO synthase (NOS) isoforms under basal and activated conditions. Using RNAseq, we uncover distinct, source-dependent effects of NO on as many as ∼10,000 genes mediated largely by S-nitrosylation. NOS enzymes and NO donors each generated unique transcriptional responses. Our data reveal non-overlapping transcriptional responses to NO that are likely mediated by distinct effectors and enzymes and highlight that NO-treated cell systems may undergo a dramatic and widespread transcriptional response.

摘要

一氧化氮（NO）的转录组学效应已在整个系统发育过程中得到广泛研究。然而，虽然基因表达通常会被NO改变，但尚未出现通用原则。在这里，我们表征了在基础和激活条件下，暴露于内源性或合成供体化合物衍生的NO或由3种不同的一氧化氮合酶（NOS）同工型产生的NO后，单一细胞类型内的基因调控情况。使用RNA测序，我们发现NO对多达约10000个基因具有独特的、依赖于来源的效应，这些效应主要由S-亚硝基化介导。NOS酶和NO供体各自产生独特的转录反应。我们的数据揭示了对NO的非重叠转录反应，这些反应可能由不同的效应器和酶介导，并突出表明经NO处理的细胞系统可能会经历剧烈且广泛的转录反应。