Extension of C. elegans lifespan using the ·NO-delivery dinitrosyl iron complexes.
J Biol Inorg Chem
; 23(5): 775-784, 2018 07.
Article
de En
| MEDLINE
| ID: mdl-29858679
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-ßgal 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.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Caenorhabditis elegans
/
Fer
/
Longévité
/
Monoxyde d'azote
/
Oxydes d'azote
Limites:
Animals
Langue:
En
Journal:
J Biol Inorg Chem
Sujet du journal:
BIOQUIMICA
Année:
2018
Type de document:
Article
Pays d'affiliation:
Taïwan