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

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 journal › Article › peer-review

16 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 language	English
Pages (from-to)	775-784
Number of pages	10
Journal	Journal of Biological Inorganic Chemistry
Volume	23
Issue number	5
DOIs	https://doi.org/10.1007/s00775-018-1569-1
State	Published - Jul 2018

Keywords

Aging
Bioinorganic chemistry
Biomedicine
Drug delivery
Nitric oxide

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10.1007/s00775-018-1569-1

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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

@article{11cdc25e4d5143cc8a6f432ed78e0f91,

title = "Extension of C. elegans lifespan using the ·NO-delivery dinitrosyl iron complexes",

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.].",

keywords = "Aging, Bioinorganic chemistry, Biomedicine, Drug delivery, Nitric oxide",

author = "Huang, {Hsiao Wen} and Lin, {Yen Hung} and Lin, {Min Hsuan} and Huang, {Ya Rong} and Chou, {Chih Hung} and Hong, {Hsiao Chin} and Wang, {Mei Ren} and Tseng, {Yu Ting} and Liao, {Po Chun} and Chung, {Min Chuan} and Ma, {Yu Jie} and Wu, {Shou Cheng} and Chuang, {Yung Jen} and Wang, {Horng Dar} and Yun-Ming Wang and Hsien-Da Huang and Lu, {Tsai Te} and Liaw, {Wen Feng}",

year = "2018",

month = jul,

doi = "10.1007/s00775-018-1569-1",

language = "English",

volume = "23",

pages = "775--784",

journal = "Journal of Biological Inorganic Chemistry",

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Huang, HW, Lin, YH, Lin, MH, Huang, YR, Chou, CH, Hong, HC, Wang, MR, Tseng, YT, Liao, PC, Chung, MC, Ma, YJ, Wu, SC, Chuang, YJ, Wang, HD, Wang, Y-M, Huang, H-D, Lu, TT & Liaw, WF 2018, 'Extension of C. elegans lifespan using the ·NO-delivery dinitrosyl iron complexes', Journal of Biological Inorganic Chemistry, vol. 23, no. 5, pp. 775-784. https://doi.org/10.1007/s00775-018-1569-1

TY - JOUR

T1 - Extension of C. elegans lifespan using the ·NO-delivery dinitrosyl iron complexes

AU - Huang, Hsiao Wen

AU - Lin, Yen Hung

AU - Lin, Min Hsuan

AU - Huang, Ya Rong

AU - Chou, Chih Hung

AU - Hong, Hsiao Chin

AU - Wang, Mei Ren

AU - Tseng, Yu Ting

AU - Liao, Po Chun

AU - Chung, Min Chuan

AU - Ma, Yu Jie

AU - Wu, Shou Cheng

AU - Chuang, Yung Jen

AU - Wang, Horng Dar

AU - Wang, Yun-Ming

AU - Huang, Hsien-Da

AU - Lu, Tsai Te

AU - Liaw, Wen Feng

PY - 2018/7

Y1 - 2018/7

N2 - 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.].

AB - 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.].

KW - Aging

KW - Bioinorganic chemistry

KW - Biomedicine

KW - Drug delivery

KW - Nitric oxide

UR - http://www.scopus.com/inward/record.url?scp=85047928696&partnerID=8YFLogxK

U2 - 10.1007/s00775-018-1569-1

DO - 10.1007/s00775-018-1569-1

M3 - Article

C2 - 29858679

AN - SCOPUS:85047928696

SN - 0949-8257

VL - 23

SP - 775

EP - 784

JO - Journal of Biological Inorganic Chemistry

JF - Journal of Biological Inorganic Chemistry

IS - 5

ER -

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

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