Aims: Very modest changes in mRNA stability can aff ect critical points in cellular energy pathways. The aim of this study was to investigate the impact of energy abundant substrates on peroxisome proliferator-activated receptors (PPARs) and PPAR-γ coactivators (PGCs) mRNA's steady-state levels.Methods: Quantitative RT-PCR study was performed to assess the eff ect of zero or normal (5 mmol/l) glucose and/or oleic acid (0.3 mmol/l) on mRNA levels of (PPARs) (PGCs) in HepG2 cells.Results: PGC-1α mRNA was signifi cantly upregulated in glucose deprived cells (123 % of the control level; p < 0.05), while PGC-1β mRNA was signifi cantly enhanced in oleate-fed cells (134 % and 160 % of control levels for zero glucose plus oleate and normal glucose plus oleate, respectively; p < 0.05) during the 0.5 h incubation. Upon the 4 h incubation, PPAR-γ1 and PGC-1α mRNAs were signifi cantly elevated in cells lacking glucose (142 % and 163 % of control levels, respectively; p < 0.05). Oleate signifi cantly suppressed PPAR-α and PGC-1β mRNA levels in glucose-deprived cells (58 % and 49 % of control levels, respectively; p < 0.05). PPAR-γ1 and -γ2 mRNAs were signifi cantly superinduced when the cells were treated with cycloheximide, whereas PPAR-α and PGC-1α and-1β mRNAs were destabilized. Upon actinomycin D treatment, glucose shortage signifi cantly stabilized PPAR-α mRNA, while PGC-1α mRNA was destabilized by oleate in glucose-deprived cells.Conclusions: Our fi ndings provide evidence that transcriptional processes that are under the control of energetic substrates are interconnected with concurrent translational processes that can change stability of mRNAs.
The effects of non-esterified fatty acids (NEFA) and hormone dehydroepiandrosterone (DHEA) on the levels of mRNAs of protein kinase C (PKC) -delta and -epsilon isoforms and those of liver fatty acid binding protein (L-FABP) were investigated in the human hepatoma HepG2 cell line. The cells were kept in low-serum, low-albumin medium during experiments. Low FA levels (100 microM) and time intervals of 4 h and 20 h were used. In these conditions, the saturated (palmitic, stearic) and monounsaturated (oleic) acids rather selectively stimulated PKC-epsilon mRNA levels. Unexpectedly, we found that these acids also suppressed liver fatty-acid binding protein (L-FABP) mRNA levels. DHEA in pharmacological doses (100 microM) produced a significant increase in PKC-delta and -epsilon mRNA levels. Although molecular mechanisms underlying the identified changes have not been investigated in this paper, our findings emphasize that NEFA-induced modulation of mRNA levels of key signalling components represent an additional mechanism for how the ambient NEFA can influence metabolic homeostasis in cells.
Chronic wounds represent a significant socio-economic problem, and the improvement of their healing is therefore an essential issue. This paper describes the preparation and biological properties of a novel functionalized nanofiber wound dressing consisting of a polycaprolactone nanofiber carrier modified by a drug delivery system, based on the lipid particles formed by 1-tetradecanol and encapsulated gentamicin and tocopherol acetate. The cytotoxicity of extracts was tested using a metabolic activity assay, and the antibacterial properties of the extracts were tested in vitro on the bacterial strains Staphylococcus aureus and Pseudomonas aeruginosa. The effect of the wound dressing on chronic wound healing was subsequently tested using a mouse model. Fourteen days after surgery, the groups treated by the examined wound cover showed a lower granulation, reepithelization, and inflammation score compared to both the uninfected groups, a lower dermis organization compared to the control, a higher scar thickness compared to the other groups, and a higher thickness of hypodermis and bacteria score compared to both the uninfected groups. This work demonstrates the basic parameters of the safety (biocompatibility) and performance (effect on healing) of the dressing as a medical device and indicates the feasibility of the concept of its preparation in outpatient conditions using a suitable functionalization device.
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