Abstract
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.
Highlights
MicroRNAs are short non-coding RNAs (18–25 nucleotides in length) that are partially complementary to the regulatory regions in the 30 - or, more rarely, 50 -untranslated region (UTRs) of targeted mRNAs or even in their coding sequences [1]
Administration of diabetogenic doses of alloxan in rats resulted in the development Administration of diabetogenic doses of alloxan in rats resulted in the development of a stable model of insulin-dependent diabetes [29]
In order to understand the molecular mechanisms associated with the reduction in blood glucose levels following SkQ1 injection, we studied the expression of genes involved in oxidative metabolism in the pancreas (Figure 4)
Summary
MicroRNAs are short non-coding RNAs (18–25 nucleotides in length) that are partially complementary to the regulatory regions in the 30 - or, more rarely, 50 -untranslated region (UTRs) of targeted mRNAs or even in their coding sequences [1]. The binding of microRNA inhibits translation of the target mRNAs or contributes to their degradation, eventually leading to gene silencing. MicroRNAs act as guides for positioning of the RNA-induced silencing complex (RISC), a molecular scaffold that facilitates interactions of microRNA with their targets, resulting in the inhibition of gene expression [2]. MicroRNAs form complex post-transcriptional regulatory networks that coordinate numerous cellular processes [3]. After the discovery of microRNAs in 1993, it has found that microRNAs affect the expression of at least 30% protein-coding genes, which makes microRNAs the most common regulators of gene expression [4].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
