No abstract

It has been observed that there is an inverse relationship between fiber size and oxidative capacity due to oxygen, ADP, and ATP diffusion limitations. We aimed to see if regular endurance exercise alongside a hypertrophic stimulus would lead to compromised adaptations to both, particularly in older animals. Here we investigated the effects of combining overload with regular endurance exercise in young (12 months) and old (26 months) male mice. The plantaris muscles of these mice were overloaded through denervation of synergists to induce hypertrophy and the mice ran on a treadmill for 30 min per day for 6 weeks. The hypertrophic response to overload was not blunted by endurance exercise, and the increase in fatigue resistance with endurance exercise was not reduced by overload. Old mice demonstrated less hypertrophy than young mice, which was associated with impaired angiogenesis and a reduction in specific tension. The data of this study suggest that combining endurance exercise and overload induces the benefits of both types of exercise without compromising adaptations to either. Additionally, the attenuated hypertrophic response to overload in old animals may be due to a diminished capacity for capillary growth.

Previous studies have demonstrated that fibre cross-sectional area (FCSA) is inversely related to oxidative capacity, which is thought to be determined by diffusion limitations of oxygen, ADP and ATP. Consequently, it is hypothesised that (1) when endurance training is combined with a hypertrophic stimulus the response to each will be blunted, and (2) muscles with a smaller FCSA will show a larger hypertrophic response than those with a large FCSA. To investigate this, we combined overload with endurance exercise in 12-month-old male mice from three different strains with different FCSA: Berlin High (BEH) (large fibres), C57BL/6J (C57) (normal-sized fibres) and Berlin Low (BEL) (small fibres). The right plantaris muscle was subjected to overload through denervation of synergists with the left muscle acting as an internal control. Half the animals trained 30 min per day for 6 weeks. The overload-induced hypertrophy was not blunted by endurance exercise, and the exercise-induced increase in fatigue resistance was not impaired by overload. All strains demonstrated similar absolute increases in FCSA, although the BEH mice with more fibres than the C57 mice demonstrated the largest increase in muscle mass and BEL mice with fewer fibres the smallest increase in muscle mass. This study suggests that endurance exercise and hypertrophic stimuli can be combined without attenuating adaptations to either modality, and that increases in FCSA are independent of baseline fibre size.

Selenium is an essential trace element that maintains normal brain function, mainly due its antioxidant properties. Although the amount of Se in the body is tightly regulated by the liver, both an excess of and deficiency in Se can modulate the cellular redox status and affect the homeostasis of other essential elements for both humans and animals. The aim of this study was to determine the effect of inorganic selenium excess on oxidative stress and iron homeostasis in brain and liver of laboratory BALB/c mice, which were supplemented with Na2SeO3 solution (0.2 mg and 0.4 mg Se/kg body weight) for 8 weeks. The content of the lipid peroxidation product malondialdehyde and antioxidant enzyme catalase activity/gene expression were used as markers of oxidative damage and were evaluated by spectrophotometric assays. Selenium and iron concentrations were determined by inductively coupled plasma mass spectrometry (ICP-MS). Catalase gene expression was analyzed by qRT-PCR and ΔΔCt methods. Our results showed that doses of 0.2 mg Se and 0.4 mg Se caused a relatively low accumulation of Se in the brain of mice; however, it induced a 10-fold increase in its accumulation in the liver and also increased iron accumulation in both tested organs. Both doses of Se increased the content of malondialdehyde as well as decreased catalase activity in the liver, while the 0.4 mg Se dose has also activated catalase gene expression. Brain of mice exposed to 0.2 mg Se showed reduced lipid peroxidation; however, the exposure to 0.4 mg of Se increased the catalase activity as well as gene expression. One may conclude that exposure to both doses of Se caused the accumulation of this micronutrient in mice brain and liver and have also provided a disrupting effect on the levels of iron. Both doses of Se have triggered oxidative liver damage. In the brain, the effect of Se was dose dependent, where −0.2 mg of Se provided antioxidant activity, which was observed through a decrease in lipid peroxidation. On the contrary, the 0.4 mg dose increased brain catalase activity as well as gene expression, which may have contributed to maintaining brain lipid peroxidation at the control level.

The interest in chemical RNA modifications is rapidly growing in the field of molecular biology. Dynamic and reversible alterations of N6-methyladenosine (m6A) RNA modification are responsible for a platter of structural and functional changes in healthy and cancerous cell states. Although many studies reported the link between tumor initiation/progression and m6A modulators, there are few studies exploring transcriptome-wide m6A profile of non-coding RNAs. The aim of current study was to identify glioma stem cell (GSC) specific m6A landscape of long non-coding RNAs (lncRNAs) applying MeRIP-seq approach. MeRIP-seq analysis assigned 77.9% of m6A peaks to mRNAs and 8.16% to lncRNAs. GSCs and differentiated cells showed 76.4% conservation of m6A peaks, while 19.4% were unique to GSCs. Seven novel GSC-specific m6A modified lncRNAs were identified: HRAT92, SLCO4A1-AS1, CEROX1, PVT1, AGAP2-AS1, MIAT, and novel lncRNA gene ENSG00000262223. Analysis disclosed a strong negative correlation between lncRNAs m6A modification rate and expression. MeRIP-seq analysis revealed m6A modifications on previously reported glioma-associated lncRNAs: LINC000461, HOTTIP, CRNDE, TUG1, and XIST. Moreover, current study disclosed that most highly m6A modified lncRNAs primarily contain m6A modifications close to 3′ and 5′ ends. Our results provide basis and insight for further studies of m6A modifications in non-coding transcriptome of GSCs.