Journal
JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY
Volume 23, Issue 5, Pages 775-784Publisher
SPRINGER
DOI: 10.1007/s00775-018-1569-1
Keywords
Nitric oxide; Biomedicine; Bioinorganic chemistry; Drug delivery; Aging
Funding
- Ministry of Science and Technology (Taiwan) [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]
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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 center dot 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) [Fe-2(mu-SR)(2)(NO)(4)] (1) as a universal platform for the O-2-triggered release of center dot NO, for the regulation of center dot NO-release kinetics (half-life = 0.6-27.4 h), and for the activation of physiological function of center dot NO. Using C. elegans as a model organism, the center dot 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-beta gal activity assay, and next-generation RNA sequencing analysis. This study unveils the anti-aging effect of center dot NO and develops DNICs as a chemical biology probe for the continued discovery of unprecedented NO physiology. [GRAPHICS] .
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