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Regulation of cyclooxygenase 2 mRNA degradation by rosiglitazone in C6 glioma cells in the presence of inflammation inductors

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Biochemistry (Moscow) Supplement Series A: Membrane and Cell Biology Aims and scope

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

References

  1. Ontaneda D., Fox R.J., Chataway J. 2015. Clinical trials in progressive multiple sclerosis: Lessons learned and future perspectives. Lancet Neurol. 14 (2), 208–223.

    Article  PubMed  Google Scholar 

  2. Anderson K.M., Olson K.E., Estes K.A., Flanagan K., Gendelman H.E., Mosley R. 2014. Dual destructive and protective roles of adaptive immunity in neurodegenerative disorders. Transl. Neurodegener. 3 (1), 25.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Heales S.J.R., Lam A.A.J., Duncan A.J., Land J. M. 2004. Neurodegeneration or neuroprotection: the pivotal role of astrocytes. Neurochem. Res. 29, 513–519.

    Article  PubMed  CAS  Google Scholar 

  4. Aleshin S., Reiser G. 2013. Role of the peroxisome proliferator-activated receptors (PPAR)-a, ß/ and ? triad in regulation of reactive oxygen species signaling in brain. Biol. Chem. 394 (12), 1553–1570.

    Article  PubMed  CAS  Google Scholar 

  5. Chistyakov D.V., Aleshin S., Sergeeva M.G., Reiser G. 2014. Regulation of peroxisome proliferator-activated receptor ß/d expression and activity levels by toll-like receptor agonists and MAP kinase inhibitors in rat astrocytes. J. Neurochem. 130 (4), 563–574.

    Article  PubMed  CAS  Google Scholar 

  6. Rampe D., Wang L., Ringheim G.E. 2004. P2X7 receptor modulation of beta-amyloidand LPSinduced cytokine secretion from human macrophages and microglia. J. Neuroimmunol. 147, 56–61.

    Article  PubMed  CAS  Google Scholar 

  7. Carta A.R. 2013. PPAR-?: Therapeutic prospects in Parkinson’s disease. Curr. Drug Targets. 14 (7), 743–751.

    Article  PubMed  CAS  Google Scholar 

  8. Štulc T., Svobodová H., Krupiková Z., Dolealová R., Marinov I., Ceška R. 2014. Rosiglitazone influences the expression of leukocyte adhesion molecules and CD14 receptor in type 2 diabetes mellitus patients. Physiol. Res./Acad. Sci. Bohemoslovaca. 63, 293–298.

    Google Scholar 

  9. Li X., Xu B., Wang Y., Wei L. 2014. Anti-inflammatory effect of peroxisome proliferator-activated receptor-? (PPAR-?) on non-obese diabetic mice with Sjogren’s syndrome. Internat. J. Clin. Exp. Pathol. 7 (8), 4886–4894.

    CAS  Google Scholar 

  10. Pisanu A., Lecca D., Mulas G., Wardas J., Simbula G., Spiga S., Carta A.R. 2014. Dynamic changes in proand anti-inflammatory cytokines in microglia after PPAR-? agonist neuroprotective treatment in the MPTPp mouse model of progressive Parkinson’s disease. Neurobiol. Disease. 71, 280–291.

    Article  CAS  Google Scholar 

  11. P óciennikowska A., Hromada-Judycka A., Borzcka K., Kwiatkowska K. 2015. Co-operation of TLR4 and raft proteins in LPS-induced pro-inflammatory signaling. Cell. Mol. Life Sci. 72 (3), 557–581.

    Article  CAS  Google Scholar 

  12. Chen X., Yang L., Zhai S. 2012. Risk of cardiovascular disease and all-cause mortality among diabetic patients prescribed rosiglitazone or pioglitazone: A meta-analysis of retrospective cohort studies. Chinese Med. J. 125 (23), 4301–4306.

    Google Scholar 

  13. Ross J.S., Jackevicius C., Krumholz H.M., Ridgeway J., Montori V.M., Alexander G.C., Shah N.D. 2012. State Medicaid programs did not make use of prior authorization to promote safer prescribing after rosiglitazone warning. Health Affairs (Project Hope). 31 (1), 188–198.

    Article  PubMed Central  Google Scholar 

  14. Luna-Medina R., Cortes-Canteli M., Alonso M., Santos A., Martinez A., Perez-Castillo A. 2005. Regulation of inflammatory response in neural cells in vitro by thiadiazolidinones derivatives through peroxisome proliferator-activated receptor gamma activation. J. Biol. Chem. 280 (22), 21453–21462.

    Article  PubMed  CAS  Google Scholar 

  15. Chistyakov D.V., Popova N.V., Grabeklis S.A., Aleshin S.E., Sergeeva M.G. 2012. Rosiglitazone as a regulator of innate immunity in a cell model of hyperglycemia. Biochemistry (Moscow) Suppl. Ser A: Membrane and Cell Biology. 6 (1), 75–81.

    Article  Google Scholar 

  16. Aleshin S., Grabeklis S., Hanck T., Sergeeva M., Reiser G. 2009. Peroxisome proliferator-activated receptor PPAR? positively controls and PPARalpha negatively controls cyclooxygenase-2 expression in rat brain astrocytes through a convergence on PPARß/d via mutual control of PPAR expression levels. Mol. Pharmacol. 76, 414–424.

    Article  PubMed  CAS  Google Scholar 

  17. Sergeeva M.G., Varfolomeeva A.T. 2006. Kaskad arakhidonovoi kisloty (Cascade of arachidonic acid). Moscow, Narodnoe obrazovanie.

    Google Scholar 

  18. Ivliev A.E., Sergeeva M.G. 2008. OrthoFocus: Program for identification of orthologs in multiple genomes in family-focused studies. J. Bioinform. Comput. Biol. 6 (4), 811–824.

    Article  PubMed  CAS  Google Scholar 

  19. Niranjan R., Kamat P.K., Nath C., Shukla R. 2010. Evaluation of guggulipid and nimesulide on production of inflammatory mediators and GFAP expression in LPS stimulated rat astrocytoma, cell line (C6). J. Ethnopharmacol. 127, 625–630.

    Article  PubMed  CAS  Google Scholar 

  20. Livak K.J., Schmittgen T.D. 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2([Delta [Delta C(T)) method. Methods (San Diego, Calif.). 25 (4), 402–408.

    Article  CAS  Google Scholar 

  21. Zhang Z.-J., Zhao L.-X., Cao D.-L., Zhang X., Gao Y.-J., Xia C. 2012. Curcumin inhibits LPSinduced CCL2 expression via JNK pathway in C6 rat astrocytoma cells. Cell. Mol.Neurobiol. 32 (6), 1003–1010.

    Article  PubMed  CAS  Google Scholar 

  22. Pérez-Ortiz J.M., Tranque P., Burgos M., Vaquero C.F., Llopis J. 2007. Glitazones induce astroglioma cell death by releasing reactive oxygen species from mitochondria: Modulation of cytotoxicity by nitric oxide. Mol. Pharmacol. 72 (2), 407–417.

    Article  PubMed  CAS  Google Scholar 

  23. Lin C.-F., Young K.-C., Bai C.-H., Yu B.-C., Ma C.-T., Chien Y.-C., Tsao C.-W. 2014. Rosiglitazone regulates anti-inflammation and growth inhibition via PTEN. BioMed Res. Int. 2014, 787924.

    PubMed  PubMed Central  Google Scholar 

  24. Anderson P. 2010. Post-transcriptional regulons coordinate the initiation and resolution of inflammation. Nat. Rev. Immunol. 10 (1), 24–35.

    Article  PubMed  CAS  Google Scholar 

  25. Ikeda Y., Yamaji R., Irie K., Kioka N., Murakami A. 2012. Glyceraldehyde-3-phosphate dehydrogenase regulates cyclooxygenase-2 expression by targeting mRNA stability. Arch. Biochem. Bbiophys. 528 (2), 141–147.

    Article  CAS  Google Scholar 

  26. Kim I., Kwak H., Lee H.K., Hyun S., Jeong S. 2012. ßCatenin recognizes a specific RNA motif in the cyclooxygenase-2 mRNA 3'-UTR and interacts with HuR in colon cancer cells. Nucl. Acids Res. 40 (14), 6863–6872.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Ross J. 1995. mRNA stability in mammalian cells. Microbiol. Rev. 59 (3), 423–450.

    PubMed  PubMed Central  CAS  Google Scholar 

  28. Khoo N.K.H., Hebbar S., Zhao W., Moore S.A., Domann F.E., Robbins M.E. 2013. Differential activation of catalase expression and activity by PPAR agonists: Implications for astrocyte protection in antiglioma therapy. Redox Biol. 1, 70–79.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Chistyakov D.V., Aleshin S.E., Astakhova A.A., Sergeeva M.G., Reiser G. 2015. Regulation of peroxisome proliferator-activated receptors PPARa and -? of rat brain astrocytes in the course of activation by toll-like receptor agonists. J. Neurochem. doi: 10.1111/jnc.13101.

    Google Scholar 

  30. Sun L., Zhang S., Jiang Z., Huang X., Wang T., Li H., Zhang L. 2011. Triptolide inhibits COX-2 expression by regulating mRNA stability in TNFa-treated A549 cells. Biochem. Biophys. Res. Commun. 416, 99–105.

    Article  PubMed  CAS  Google Scholar 

  31. Subramaniam D., Ramalingam S., Linehan D.C., Dieckgraefe B.K., Anant S. 2011. RNA binding protein CUGBP2/CELF2 mediates curcumin-induced mitotic catastrophe of pancreatic cancer cells. PLoS One. 6.

    Google Scholar 

  32. Frey M.R., Hilliard V.C., Mullane M.T., Polk D.B. 2010. ErbB4 promotes cyclooxygenase-2 expression and cell survival in colon epithelial cells. Lab. Investigation. J. Tech. Meth. Pathol. 90 (10), 1415–1424.

    Article  CAS  Google Scholar 

  33. Monick M.M., Robeff P.K., Butler N.S., Flaherty D.M., Carter A.B., Peterson M.W., Hunninghake G.W. 2002. Phosphatidylinositol 3-kinase activity negatively regulates stability of cyclooxygenase 2 mRNA. J. Biol. Chem. 277, 32992–33000.

    Article  PubMed  CAS  Google Scholar 

  34. Mancini A.D., Di Battista J.A. 2011. The cardinal role of the phospholipase A(2)/cyclooxygenase-2/prostaglandin E synthase/prostaglandin E2 (PCPP) axis in inflammostasis. Inflamm. Res. 60 (12), 1083–1092.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Faculty of Bioengineering and Bioinformatics, Moscow Lomonosov State University, Leninskie Gory, 1, build. 73, Moscow, 119234, Russia

    E. V. Pankevich

  2. Belozersky Institute of Physico-Chemical Biology, Moscow Lomonosov State University, Leninskie Gory, 1, build 40, Moscow, 119992, Russia

    D. V. Chistyakov, A. A. Astakhova, O. S. Strelkova & M. G. Sergeeva

Authors
  1. E. V. Pankevich
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  2. D. V. Chistyakov
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  3. A. A. Astakhova
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  4. O. S. Strelkova
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  5. M. G. Sergeeva
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Correspondence to D. V. Chistyakov.

Additional information

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

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