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*

*Corresponding author for this work

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

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.].

Original languageEnglish
Pages (from-to)775-784
Number of pages10
JournalJournal of Biological Inorganic Chemistry
Volume23
Issue number5
DOIs
StatePublished - 1 Jul 2018

Keywords

  • Aging
  • Bioinorganic chemistry
  • Biomedicine
  • Drug delivery
  • Nitric oxide

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    Huang, H. W., Lin, Y. H., Lin, M. H., Huang, Y. R., Chou, C. H., Hong, H. C., Wang, M. R., Tseng, Y. T., Liao, P. C., Chung, M. C., Ma, Y. J., Wu, S. C., Chuang, Y. J., Wang, H. D., Wang, Y-M., Huang, H. D., Lu, T. T., & Liaw, W. F. (2018). Extension of C. elegans lifespan using the ·NO-delivery dinitrosyl iron complexes. Journal of Biological Inorganic Chemistry, 23(5), 775-784. https://doi.org/10.1007/s00775-018-1569-1