Effect of high-intensity interval training on expression of microRNA-149 and genes regulating mitochondrial biogenesis in doxorubicin-cardiotoxicity in rats
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We have investigated the effect of high-intensity interval exercise (HIIT) on DOX-induced cardiotoxicity and the expression of mitochondrial biogenesis genes SIRT-1, PGC-1α, and NRF-2 as well as microRNA-149-5p in a rat model. Twenty-four male Wistar rats (250–270 g) were randomly divided in four groups (n = 6/each): control, HIIT, DOX, and HIIT+DOX. HIIT was performed on a treadmill as seven alternative intervals of high and low intensity trainings for 1 h a day for 6 weeks. After the last session of HIIT, DOX was injected i.p. to trained and time-matched control rats. After 3 days, the blood and heart samples were obtained. The plasma levels of myocardial creatine kinase (CK-MB) were measured using ELISA kit. The tissue homogenates were used to determine the expression of genes and microRNA via real-time PCR method. DOX administration significantly increased CK-MB levels and reduced the expression levels of SIRT-1 and PGC-1α in comparison to control group. Prior treatment of DOX-received rats with HIIT protocol significantly reduced the CK-MB release and upregulated the expression profiles of SIRT-1, PGC-1α, and NRF-2 toward control values. In addition, DOX toxicity significantly increased the expression level of microRNA-149 comparing to control rats and HIIT reversed the expression of this microRNA in DOX-received rats. Our data suggested that DOX-induced cardiotoxicity could be, at least in part, due to impaired SIRT-1/PGC-1α/NRF-2 genes regulating mitochondrial biogenesis and microRNA-149 dysregulation. However, prior training of rats with HIIT had protective effect on DOX cardiotoxicity through reversing the expression profiles of these genes and microRNA.
KeywordsInterval training Mitochondrial function microRNA SIRT PGC-1α Exercise
This study was the thesis of Parisa Zare.
This study was supported by a grant number 1395.652 from Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
The study was approved by the Animal Experimentation Ethics Committee of Tabriz University of Medical Sciences, Tabriz, Iran (code number 506714).
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