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

doi:10.1007/s00775-018-1569-1

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

J Biol Inorg Chem. 2018 Jul;23(5):775-784. doi: 10.1007/s00775-018-1569-1. Epub 2018 Jun 1.

Authors

Hsiao-Wen Huang¹, Yen-Hung Lin², Min-Hsuan Lin³, Ya-Rong Huang⁴, Chih-Hung Chou⁴, Hsiao-Chin Hong⁴, Mei-Ren Wang⁵, Yu-Ting Tseng⁵, Po-Chun Liao⁵, Min-Chuan Chung⁵, Yu-Jie Ma⁵, Shou-Cheng Wu⁶, Yung-Jen Chuang⁷, Horng-Dar Wang⁸, Yun-Ming Wang⁹, Hsien-Da Huang¹⁰, Tsai-Te Lu^{11

12}, Wen-Feng Liaw¹³

Affiliations

¹ Department of Chemistry, National Tsing Hua University, Hsinchu, 30013, Taiwan.
² Institute of Biotechnology, National Tsing Hua University, Hsinchu, 30013, Taiwan.
³ Department of Medical Science and Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, 30013, Taiwan.
⁴ Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu, 30013, Taiwan.
⁵ Department of Chemistry, Chung Yuan Christian University, Taoyuan, 32023, Taiwan.
⁶ Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, 30013, Taiwan.
⁷ Department of Medical Science and Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, 30013, Taiwan. yjchuang@life.nthu.edu.tw.
⁸ Institute of Biotechnology, National Tsing Hua University, Hsinchu, 30013, Taiwan. hdwang@life.nthu.edu.tw.
⁹ Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, 30013, Taiwan. ymwang@mail.nctu.edu.tw.
¹⁰ Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu, 30013, Taiwan. bryan@mail.nctu.edu.tw.
¹¹ Department of Chemistry, Chung Yuan Christian University, Taoyuan, 32023, Taiwan. TTLu@cycu.edu.tw.
¹² Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, 30013, Taiwan. TTLu@cycu.edu.tw.
¹³ Department of Chemistry, National Tsing Hua University, Hsinchu, 30013, Taiwan. wfliaw@mx.nthu.edu.tw.

PMID: 29858679
DOI: 10.1007/s00775-018-1569-1

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.

Keywords: Aging; Bioinorganic chemistry; Biomedicine; Drug delivery; Nitric oxide.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenylate Kinase / metabolism
Animals
Caenorhabditis elegans / genetics
Caenorhabditis elegans / physiology*
Half-Life
Iron / chemistry*
Kinetics
Longevity*
Molecular Structure
Nitric Oxide / administration & dosage*
Nitric Oxide / chemistry
Nitrogen Oxides / chemistry*
Sequence Analysis, RNA
Signal Transduction
Spectrum Analysis / methods

Substances

Nitrogen Oxides
Nitric Oxide
dinitrosyl iron complex
Iron
Adenylate Kinase