CO ameliorates endothelial senescence induced by 5-fluorouracil through SIRT1 activation.
Endothelial senescence is the main risk factor that contributes to vascular dysfunction and the progression of vascular disease. Carbon monoxide (CO) plays an important role in preventing vascular dysfunction and in maintaining vascular physiology or homeostasis. The application of exogenous CO has been shown to confer protection in several models of cardiovascular injury or disease, including hypertension, atherosclerosis, balloon-catheter injury, and graft rejection. However, the mechanism by which CO prevents endothelial senescence has been largely unexplored. The aim of this study was to evaluate the effects of CO on endothelial senescence and to investigate the possible mechanisms underlying this process. We measured the levels of senescence-associated-β-galactosidase activity, senescence-associated secretory phenotype, reactive oxygen species (ROS) production, and stress granule in human umbilical vein endothelial cells and the WI-38 human diploid fibroblast cell line. We found that 5-fluorouracil (5FU)-induced ROS generation was inhibited by CO-releasing molecules (CORM)-A1 treatment, and endothelial senescence induced by 5FU was attenuated by CORM-A1 treatment. The SIRT1 inhibitor EX527 reversed the inhibitory effect of CO on the 5FU-induced endothelial senescence. Furthermore, SIRT1 deficiency abolished the stress granule formation by CO. Our results suggest that CO alleviates the endothelial senescence induced by 5FU through SIRT1 activation and may hence have therapeutic potential for the treatment of vascular diseases.
['Zheng|Min|M|', 'Chen|Yubing|Y|', 'Park|Jeongmin|J|', 'Song|Hyun-Chul|HC|', 'Chen|Yingqing|Y|', 'Park|Jeong Woo|JW|', 'Joe|Yeonsoo|Y|', 'Chung|Hun Taeg|HT|']
D000975:Antioxidants D002248:Carbon Monoxide D016922:Cellular Senescence D015536:Down-Regulation D005472:Fluorouracil D051547:Heme Oxygenase-1 D061307:Human Umbilical Vein Endothelial Cells D006801:Humans D052250:Nitric Oxide Synthase Type III D017382:Reactive Oxygen Species D056564:Sirtuin 1
Endothelial senescence 5-Fluorouracil SIRT1 Carbon monoxide Reactive oxygen species