Abstract
It has recently become clear that regulation of mRNA stability plays an important role in the development of cell responses to stimulation of toll-like receptors during inflammation. This discovery motivated a search for low molecular weight substances modulating the stability of mRNA encoding proteins involved in inflammatory responses. In this work, regulation of the cyclooxygenase 2 (COX-2) expression by rosiglitazone–a promising drug for regulation of inflammation–was studied on rat glioma cell line C6. Inflammatory response was induced by lipopolysaccaride (LPS). The concentration of prostaglandin E2 (PGE2) was measured by ELISA, the level of COX-2 mRNA was determined by real-time PCR. It was shown that treatment with LPS caused a 6-fold increase in the PGE2 synthesis, which correlated with an increase in the COX-2 mRNA expression. Rosiglitazone induced a 2-fold decrease of the LPS-stimulated PGE2 release and reduced the levels of COX-2 transcripts. To explore the molecular mechanisms of the rosiglitazone effect, we estimated the stability of COX-2 mRNA. Cells were incubated in the presence of LPS for 1 h, and then de novo mRNA transcription was blocked with actinomycin D. The levels of mRNA were determined at various time points. Treatment with rosiglitazone was carried out for 30 min before the LPS addition. The COX-2 mRNA half-life in native cells was found to be 75 min. LPS stimulation slowed down the mRNA degradation so that its half-life time was 120 min, and the treatment with rosiglitazone restored this process back to the normal level. The results suggest that rosiglitazone regulates the stability of COX-2 mRNA. This opens up new perspectives for therapeutic applications of this drug.
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Abbreviations
- CNS:
-
central neural system
- COX-2:
-
cyclooxygenase 2
- LPS:
-
lipopolysaccharide
- PGE2 :
-
prostaglandin E2
- RG:
-
rosiglitazone
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Original Russian Text © E.V. Pankevich, D.V. Chistyakov, A.A. Astakhova, O.S. Strelkova, M.G. Sergeeva, 2015, published in Biologicheskie Membrany, 2015, Vol. 32, No. 5–6, pp. 373–378.
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Pankevich, E.V., Chistyakov, D.V., Astakhova, A.A. et al. Regulation of cyclooxygenase 2 mRNA degradation by rosiglitazone in C6 glioma cells in the presence of inflammation inductors. Biochem. Moscow Suppl. Ser. A 9, 337–341 (2015). https://doi.org/10.1134/S1990747815050086
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DOI: https://doi.org/10.1134/S1990747815050086