Extension of C. elegans lifespan using the ·NO-delivery dinitrosyl iron complexes

Hsiao Wen Huang, Yen Hung Lin, Min Hsuan Lin, Ya Rong Huang, Chih Hung Chou, Hsiao Chin Hong, Mei Ren Wang, Yu Ting Tseng, Po Chun Liao, Min Chuan Chung, Yu Jie Ma, Shou Cheng Wu, Yung Jen Chuang, Horng Dar Wang, Yun-Ming Wang, Hsien-Da Huang, Tsai Te Lu, Wen Feng Liaw*

*此作品的通信作者

研究成果: Article同行評審

17 引文 斯高帕斯(Scopus)

摘要

Abstract: The ubiquitous and emerging physiology function of endogenous nitric oxide in vascular, myocardial, immune, and neuronal systems prompts chemists to develop a prodrug for the controlled delivery of ·NO in vivo and for the translational biomedical application. Inspired by the discovery of natural [Fe(NO)2] motif, herein, we develop the synthetic dinitrosyl iron complexes (DNICs) [Fe2(μ-SR)2(NO)4] (1) as a universal platform for the O2-triggered release of ·NO, for the regulation of ·NO-release kinetics (half-life = 0.6–27.4 h), and for the activation of physiological function of ·NO. Using C. elegans as a model organism, the ·NO-delivery DNIC 1 regulates IIS signaling pathway, AMPK signaling pathway, and mitochondrial function pathway to extend the lifespan and to delay the aging process based on the lifespan analysis, SA-βgal activity assay, and next-generation RNA sequencing analysis. This study unveils the anti-aging effect of ·NO and develops DNICs as a chemical biology probe for the continued discovery of unprecedented NO physiology. Graphical abstract: [Figure not available: see fulltext.].

原文English
頁(從 - 到)775-784
頁數10
期刊Journal of Biological Inorganic Chemistry
23
發行號5
DOIs
出版狀態Published - 7月 2018

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