a Department of Radiology, The Geisel School of Medicine, Dartmouth College, Lebanon, New Hampshire 03756.
b Laboratory of Radiation Biology, Department of Applied Veterinary Sciences, Division of Veterinary Medicine, Faculty of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.
Radiat Res. 2018 May;189(5):519-528. doi: 10.1667/RR14781.1. Epub 2018 Feb 23.
Endothelial nitric oxide synthase (eNOS), a constitutive enzyme expressed in vascular endothelial cells, is the main source of nitric oxide (NO), which plays key roles in diverse biological functions, including regulation of vascular tone. Exposure to radiation has been known to generate nitric oxide from eNOS; however, the precise mechanism of its generation and function is not known. The goal of this study was to determine the involvement of radiation-induced DNA damage response (DDR) on eNOS transcription and its effect on cell survival after irradiation. Irradiated bovine aortic endothelial cells showed increased eNOS transcription and NO generation through upregulation of ataxia-telangiectasia mutated (ATM) kinase. Radiation exposure induced NO inhibited cell death, as well as induced cellular senescence postirradiation. This study established that radiation-induced DDR uses ATM kinase to upregulate eNOS transcription and NO generation, leading to cellular senescence, which may play a critical role in radiation-mediated cardiovascular injury.
内皮型一氧化氮合酶（eNOS）是一种在血管内皮细胞中表达的组成型酶，是一氧化氮（NO）的主要来源，在多种生物学功能中发挥关键作用，包括调节血管张力。已知辐射会从 eNOS 产生一氧化氮；然而，其产生和功能的确切机制尚不清楚。本研究的目的是确定辐射诱导的 DNA 损伤反应（DDR）对 eNOS 转录的参与及其对照射后细胞存活的影响。照射后的牛主动脉内皮细胞通过共济失调毛细血管扩张突变（ATM）激酶的上调显示出 eNOS 转录和 NO 生成的增加。辐射暴露诱导的 NO 抑制细胞死亡，并在照射后诱导细胞衰老。这项研究确立了辐射诱导的 DDR 使用 ATM 激酶来上调 eNOS 转录和 NO 生成，导致细胞衰老，这可能在辐射介导的心血管损伤中起关键作用。
