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Regulation of Cyclooxygenase 2 mRNA Degradation by Rosiglitazone in C6 Glioma Cells in the Presence of Inflammation Inductorsстатья
Информация о цитировании статьи получена из
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 18 марта 2016 г.
- Авторы: Pankevich E.V., Chistyakov D.V., Astakhova A.A., Strelkova O.S., Sergeeva M.G.
- Журнал: Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology
- Том: 9
- Номер: 4
- Год издания: 2015
- Издательство: Pleiades Publishing, Ltd
- Местоположение издательства: Road Town, United Kingdom
- Первая страница: 337
- Последняя страница: 341
- DOI: 10.1134/S1990747815050086
- Аннотация: It has recently become clear that regulation of mRNA stability plays an important role in the development of cell responses to stimulation of tolllike receptors during inflammation. This discovery moti vated 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 (COX2) 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 COX2 mRNA was determined by realtime PCR. It was shown that treatment with LPS caused a 6fold increase in the PGE2 synthesis, which correlated with an increase in the COX2 mRNA expression. Rosiglitazone induced a 2fold decrease of the LPSstimulated PGE2 release and reduced the levels of COX2 transcripts. To explore the molecular mechanisms of the rosiglitazone effect, we estimated the stability of COX2 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 COX2 mRNA halflife in native cells was found to be 75 min. LPS stimulation slowed down the mRNA degradation so that its halflife 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 COX2 mRNA. This opens up new perspectives for therapeutic applications of this drug.
- Добавил в систему: Панкевич Евгения Вадимовна