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Mechanisms of superinduction for PPARalpha, PPARgamma, PPARbeta expression in astrocytesтезисы доклада
- Авторы: Chistyakov Dmitry V., Georg Reiser, Sergeeva Marina G.
- Сборник: Nuclear receptors: Linking molecules, genomes & physiology
- Тезисы
- Год издания: 2013
- Первая страница: 128
- Последняя страница: 128
- Аннотация: Superinduction is a phenomenon of a gene expression increase in the presence of inhibitors of protein synthesis. This was described for cyclooxygenase 2, interleukin 6, transcription factor SOX9. Our data allow to add PPARs to this list. We compare PPARa, y and [3/8 expression after cycloheximide addition to the LPS-stimulated and naïve astrocytes and estimated the gene mRNA expression at 4 h. The administration of cycloheximide alone induced 6-fold increase of PPARa and PPAR13/6 and 3-fold increase of PPARy expression levels. This means that there are labile proteins that normally suppresses mRNA PPARs expression. A labile protein could influence the mRNA stability or the promoter of a gene could have an influence a mRNA transcription. Estimation of mRNA stability with the transcriptional inhibitor actinomycin D revealed that PPARa and PPARI3/15 are more stable than reference gene GAPDH, while mRNA PPARy totally degraded after 4 h actinomycin D treatment. Further we compared cycloheximide influence on LPS-stimulated mRNA PPARa and PPARy decrease and mRNA PPARB/S increase. Expression of mRNA COX-2 was used as reference gene with well-described mechanism of superinduction. There are multiple regulation points of PPARs expression dependence from protein synthesis in naïve and LPS-stimulated astrocytes with involvement of NF-kB, p38, JNK inhibitors Bay 11-7085, SB203580, SP600125, respectively. Taken together, mRNA PPARs expression profiles are regulated via labile proteins, their roles changed in course of cellular response to LPS, the labile regulatory proteins for each PPARs have different sensitivity for tested inhibitors. This work was supported by grants 12-04-32133, 13-04-00833a.
- Добавил в систему: Чистяков Дмитрий Викторович