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.
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Acknowledgments
We gratefully acknowledge the support on confocal microscope from the Department of Bioscience Technology at Chung Yuan Christian University (Mr. Jhe-Jhih Lin) and the Department of Biological Science and Technology at National Chiao Tung University, and on ICP-MS from the Department of Biomedical Engineering and Environmental Science at National Tsing Hua University. We are indebted to the facilities of the C. elegans Core Facility Taiwan. We also thank the Ministry of Science and Technology (Taiwan) for financial support by Grant MOST 102-2113-M-033-009-MY2, MOST 103-2632-M-033-001-MY3, MOST 104-2113-M-033-005-MY2, MOST 106-2113-M-007-028-MY2. We also thank Dr. Lawrence Yu-Min Liu for valuable discussion.
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Huang, HW., Lin, YH., Lin, MH. et al. Extension of C. elegans lifespan using the ·NO-delivery dinitrosyl iron complexes. J Biol Inorg Chem 23, 775–784 (2018). https://doi.org/10.1007/s00775-018-1569-1
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DOI: https://doi.org/10.1007/s00775-018-1569-1