Development of a novel molecular probe for the detection of liver mitochondrial redox metabolism

Abstract Redox status influences the course of the inflammatory, metabolic, and proliferative liver diseases. Oxidative stress is thought to play a crucial and sustained role in the pathological progression of early steatosis to severe hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Ox...

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Autores principales:	Md. Zahangir Hosain, Fuminori Hyodo, Takeshi Mori, Koyo Takahashi, Yusuke Nagao, Hinako Eto, Masaharu Murata, Tomohiko Akahoshi, Masayuki Matsuo, Yoshiki Katayama
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d7b4042cffb2419d898ba3cab0fe5402
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spelling	oai:doaj.org-article:d7b4042cffb2419d898ba3cab0fe54022021-12-02T18:37:07ZDevelopment of a novel molecular probe for the detection of liver mitochondrial redox metabolism10.1038/s41598-020-73336-12045-2322https://doaj.org/article/d7b4042cffb2419d898ba3cab0fe54022020-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-73336-1https://doaj.org/toc/2045-2322Abstract Redox status influences the course of the inflammatory, metabolic, and proliferative liver diseases. Oxidative stress is thought to play a crucial and sustained role in the pathological progression of early steatosis to severe hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Oxidative stress induced by reactive oxygen species which are generated in the mitochondria can lead to chronic organelle damage in hepatocytes. Currently, the diagnosis of liver disease requires liver biopsy, which is invasive and associated with complications. The present report describes the development of a novel molecular probe, EDA-PROXYL, with higher reactivity and mitochondrial selectivity than standard carboxyl-PROXYL and carbamoyl-PROXYL probes. The membrane permeability of our probe improved in aqueous environments which led to increased accumulation in the liver and interaction of EDA-PROXYL with the carnitine transporter via the amine (NH3 +) group further increased accumulation. This increased mitochondrial sensitivity and enhanced accumulation highlight the potential of EDA-PROXYL as a molecular probe for determining metabolic reactions of the mitochondria. Thus, this novel probe could be a tool for the evaluation of redox status of the mitochondria to assess the degree of liver injury and, ultimately, the response to pharmacological therapy.Md. Zahangir HosainFuminori HyodoTakeshi MoriKoyo TakahashiYusuke NagaoHinako EtoMasaharu MurataTomohiko AkahoshiMasayuki MatsuoYoshiki KatayamaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-8 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Md. Zahangir Hosain Fuminori Hyodo Takeshi Mori Koyo Takahashi Yusuke Nagao Hinako Eto Masaharu Murata Tomohiko Akahoshi Masayuki Matsuo Yoshiki Katayama Development of a novel molecular probe for the detection of liver mitochondrial redox metabolism
description	Abstract Redox status influences the course of the inflammatory, metabolic, and proliferative liver diseases. Oxidative stress is thought to play a crucial and sustained role in the pathological progression of early steatosis to severe hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Oxidative stress induced by reactive oxygen species which are generated in the mitochondria can lead to chronic organelle damage in hepatocytes. Currently, the diagnosis of liver disease requires liver biopsy, which is invasive and associated with complications. The present report describes the development of a novel molecular probe, EDA-PROXYL, with higher reactivity and mitochondrial selectivity than standard carboxyl-PROXYL and carbamoyl-PROXYL probes. The membrane permeability of our probe improved in aqueous environments which led to increased accumulation in the liver and interaction of EDA-PROXYL with the carnitine transporter via the amine (NH3 +) group further increased accumulation. This increased mitochondrial sensitivity and enhanced accumulation highlight the potential of EDA-PROXYL as a molecular probe for determining metabolic reactions of the mitochondria. Thus, this novel probe could be a tool for the evaluation of redox status of the mitochondria to assess the degree of liver injury and, ultimately, the response to pharmacological therapy.
format	article
author	Md. Zahangir Hosain Fuminori Hyodo Takeshi Mori Koyo Takahashi Yusuke Nagao Hinako Eto Masaharu Murata Tomohiko Akahoshi Masayuki Matsuo Yoshiki Katayama
author_facet	Md. Zahangir Hosain Fuminori Hyodo Takeshi Mori Koyo Takahashi Yusuke Nagao Hinako Eto Masaharu Murata Tomohiko Akahoshi Masayuki Matsuo Yoshiki Katayama
author_sort	Md. Zahangir Hosain
title	Development of a novel molecular probe for the detection of liver mitochondrial redox metabolism
title_short	Development of a novel molecular probe for the detection of liver mitochondrial redox metabolism
title_full	Development of a novel molecular probe for the detection of liver mitochondrial redox metabolism
title_fullStr	Development of a novel molecular probe for the detection of liver mitochondrial redox metabolism
title_full_unstemmed	Development of a novel molecular probe for the detection of liver mitochondrial redox metabolism
title_sort	development of a novel molecular probe for the detection of liver mitochondrial redox metabolism
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/d7b4042cffb2419d898ba3cab0fe5402
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Development of a novel molecular probe for the detection of liver mitochondrial redox metabolism

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