Mitochondrial Antioxidant SkQ1 Has a Beneficial Effect in Experimental Diabetes as Based on the Analysis of Expression of microRNAs and mRNAs for the Oxidative Metabolism Regulators

Diabetes mellitus and related complications are among the most important problems of the world-leading healthcare systems. Despite their priority, molecular and genetic aspects of diabetes pathogenesis are poorly understood; however, the involvement of oxidative stress in this process is undoubted....

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Autores principales:	Yuliya Dvoretskaya, Victor Glanz, Mariya Gryaznova, Mikhail Syromyatnikov, Vasily Popov
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	mitochondria-targeted antioxidant microRNA oxidative stress 10-(6′-plastoquinonyl)decyltriphenylphosphonium qPCR gene expression Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/2a120dd58c924f3d8a8d97f413ef8175
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spelling	oai:doaj.org-article:2a120dd58c924f3d8a8d97f413ef81752021-11-25T16:27:46ZMitochondrial Antioxidant SkQ1 Has a Beneficial Effect in Experimental Diabetes as Based on the Analysis of Expression of microRNAs and mRNAs for the Oxidative Metabolism Regulators10.3390/antiox101117492076-3921https://doaj.org/article/2a120dd58c924f3d8a8d97f413ef81752021-10-01T00:00:00Zhttps://www.mdpi.com/2076-3921/10/11/1749https://doaj.org/toc/2076-3921Diabetes mellitus and related complications are among the most important problems of the world-leading healthcare systems. Despite their priority, molecular and genetic aspects of diabetes pathogenesis are poorly understood; however, the involvement of oxidative stress in this process is undoubted. Rats with experimental diabetes induced by the intraperitoneal injection of alloxan were subjected to the antioxidant pre-therapy with a series of mitochondria-targeted 10-(6’-plastoquinonyl)decyltriphenylphosphonium (SkQ1) injections and analyzed for the expression of mRNAs and microRNAs by real-time quantitative polymerase chain reaction to identify potential predictors of diabetes. Animals that received SkQ1 before diabetes induction demonstrated lower blood glucose levels compared to the diabetic animals not subjected to the therapy. SkQ1 caused changes in the mRNA levels of genes involved in the cellular defense against free radicals, which indicates a beneficial effect of the pre-therapy. Moreover, similar changes were observed on the epigenetic level, as the microRNA expression patterns not only proved the SkQ1 efficacy but also correlated with the expression levels of their mRNA targets. Oxidative stress and macromolecule damage by free radicals are determining factors in diabetes, which suggests that strategies aimed at restoring the antioxidant status of the cell can be beneficial. Mitochondria-targeted antioxidant SkQ1 demonstrates positive effects on several levels, from the normalization of the blood glucose content to genetic and epigenetic changes. Our results can serve as a basis for the development of novel therapeutic and diagnostic strategies.Yuliya DvoretskayaVictor GlanzMariya GryaznovaMikhail SyromyatnikovVasily PopovMDPI AGarticlemitochondria-targeted antioxidantmicroRNAoxidative stress10-(6′-plastoquinonyl)decyltriphenylphosphoniumqPCRgene expressionTherapeutics. PharmacologyRM1-950ENAntioxidants, Vol 10, Iss 1749, p 1749 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	mitochondria-targeted antioxidant microRNA oxidative stress 10-(6′-plastoquinonyl)decyltriphenylphosphonium qPCR gene expression Therapeutics. Pharmacology RM1-950
spellingShingle	mitochondria-targeted antioxidant microRNA oxidative stress 10-(6′-plastoquinonyl)decyltriphenylphosphonium qPCR gene expression Therapeutics. Pharmacology RM1-950 Yuliya Dvoretskaya Victor Glanz Mariya Gryaznova Mikhail Syromyatnikov Vasily Popov Mitochondrial Antioxidant SkQ1 Has a Beneficial Effect in Experimental Diabetes as Based on the Analysis of Expression of microRNAs and mRNAs for the Oxidative Metabolism Regulators
description	Diabetes mellitus and related complications are among the most important problems of the world-leading healthcare systems. Despite their priority, molecular and genetic aspects of diabetes pathogenesis are poorly understood; however, the involvement of oxidative stress in this process is undoubted. Rats with experimental diabetes induced by the intraperitoneal injection of alloxan were subjected to the antioxidant pre-therapy with a series of mitochondria-targeted 10-(6’-plastoquinonyl)decyltriphenylphosphonium (SkQ1) injections and analyzed for the expression of mRNAs and microRNAs by real-time quantitative polymerase chain reaction to identify potential predictors of diabetes. Animals that received SkQ1 before diabetes induction demonstrated lower blood glucose levels compared to the diabetic animals not subjected to the therapy. SkQ1 caused changes in the mRNA levels of genes involved in the cellular defense against free radicals, which indicates a beneficial effect of the pre-therapy. Moreover, similar changes were observed on the epigenetic level, as the microRNA expression patterns not only proved the SkQ1 efficacy but also correlated with the expression levels of their mRNA targets. Oxidative stress and macromolecule damage by free radicals are determining factors in diabetes, which suggests that strategies aimed at restoring the antioxidant status of the cell can be beneficial. Mitochondria-targeted antioxidant SkQ1 demonstrates positive effects on several levels, from the normalization of the blood glucose content to genetic and epigenetic changes. Our results can serve as a basis for the development of novel therapeutic and diagnostic strategies.
format	article
author	Yuliya Dvoretskaya Victor Glanz Mariya Gryaznova Mikhail Syromyatnikov Vasily Popov
author_facet	Yuliya Dvoretskaya Victor Glanz Mariya Gryaznova Mikhail Syromyatnikov Vasily Popov
author_sort	Yuliya Dvoretskaya
title	Mitochondrial Antioxidant SkQ1 Has a Beneficial Effect in Experimental Diabetes as Based on the Analysis of Expression of microRNAs and mRNAs for the Oxidative Metabolism Regulators
title_short	Mitochondrial Antioxidant SkQ1 Has a Beneficial Effect in Experimental Diabetes as Based on the Analysis of Expression of microRNAs and mRNAs for the Oxidative Metabolism Regulators
title_full	Mitochondrial Antioxidant SkQ1 Has a Beneficial Effect in Experimental Diabetes as Based on the Analysis of Expression of microRNAs and mRNAs for the Oxidative Metabolism Regulators
title_fullStr	Mitochondrial Antioxidant SkQ1 Has a Beneficial Effect in Experimental Diabetes as Based on the Analysis of Expression of microRNAs and mRNAs for the Oxidative Metabolism Regulators
title_full_unstemmed	Mitochondrial Antioxidant SkQ1 Has a Beneficial Effect in Experimental Diabetes as Based on the Analysis of Expression of microRNAs and mRNAs for the Oxidative Metabolism Regulators
title_sort	mitochondrial antioxidant skq1 has a beneficial effect in experimental diabetes as based on the analysis of expression of micrornas and mrnas for the oxidative metabolism regulators
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/2a120dd58c924f3d8a8d97f413ef8175
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Mitochondrial Antioxidant SkQ1 Has a Beneficial Effect in Experimental Diabetes as Based on the Analysis of Expression of microRNAs and mRNAs for the Oxidative Metabolism Regulators

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