Skip to main content
SpringerLink
Log in

Aspirin-induced apoptosis in Jurkat cells is not mediated by peroxisome proliferator-activated receptor delta

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Nonsteroidal antiinflammatory drugs may induce apoptosis via inhibition of peroxisome proliferator-activated receptor delta (PPARδ) activity. Here we analyze the role of PPARδ in aspirin-induced apoptosis of Jurkat cells, which, together with other lymphoid cell lines, express PPARδ mRNA. Aspirin increased PPARδ mRNA levels in Jurkat cells, but decreased the activity of both PPARδ and PPARα/γ, assayed using the luciferase reporter constructs DRE and ACO, respectively. The DNA binding of PPARδ was not affected by 10 mM aspirin, which induces apoptosis in Jurkat cells. Moreover, neither addition of a specific ligand of PPARδ nor transient transfection of PPARδ expression vectors protected Jurkat cells from aspirin-induced apoptosis. These results indicate that PPARδ is not involved in aspirin-induced apoptosis. Therefore, the mechanism by which aspirin mediates cell death in Jurkat cells remains unknown (Mol Cell Biochem 266: 57–63, 2004)

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Lauer MS: Clinical practice. Aspirin for primary prevention of coronary events. N Engl J Med 346: 1468–1474, 2002

    Google Scholar 

  2. Huls G, Koorstra JJ, Kleibeuker, JH: Non-steroidal anti-inflammatory drugs and molecular carcinogenesis of colorectal carcinomas. Lancet 362: 230–232, 2003

    Google Scholar 

  3. Vane JR, Bakhle YS, Botting RM: Cyclooxygenases 1 and 2. Annu Rev Pharmacol Toxicol 38: 97–120, 1998.

    Google Scholar 

  4. Shiff SJ, Rigas B: Nonsteroidal anti-inflammatory drugs and colorectal cancer: Evolving concepts of their chemopreventive actions. Gastroenterology 113: 1992–1998, 1997

    Google Scholar 

  5. Tegeder I, Pfeilschifter J, Geisslinger G: Cyclooxygenase-independent actions of cyclooxygenase inhibitors. FASEB J 15: 2057–2072, 2001

    Google Scholar 

  6. Chan, TA: Nonsteroidal anti-inflammatory drugs, apoptosis, and colon-cancer chemoprevention. Lancet Oncol 3: 166–174, 2002

    Google Scholar 

  7. Castaño E, Dalmau M, Barragán M, Pueyo G, Bartrons R, Gil J: Aspirin induces cell death and caspase-dependent phosphatidylserine externalization in HT-29 human colon adenocarcinoma cells. Br J Cancer 81: 294–299, 1999

    Google Scholar 

  8. Bellosillo B, Piqué M, Barragán M, Castaño E, Villamor N, Colomer D, Montserrat E, Pons G, Gil J: Aspirin and salicylate induce apoptosis and activation of caspases in B-cell chronic lymphocytic leukemia cells. Blood 92: 1406–1414, 1998

    Google Scholar 

  9. Piqué M, Barragán M, Dalmau M, Bellosillo B, Pons G, Gil J: Aspirin induces apoptosis through mitochondrial cytochrome c release. FEBS Lett 480: 193–196, 2000

    Google Scholar 

  10. Yamamoto Y, Yin MJ, Lin KM, Gaynor RB: Sulindac inhibits activation of the NF-kappaB pathway. J Biol Chem 274: 27307–27314, 1999

    Google Scholar 

  11. Liptay S, Bachem M, Hacker G, Adler G, Debatin KM, Schmid RM: Inhibition of nuclear factor kappa B and induction of apoptosis in T-lymphocytes by sulfasalazine. Br J Pharmacol 128: 1361–1369, 1999

    Google Scholar 

  12. Stark LA, Din FV, Zwacka RM, Dunlop MG:Aspirin-induced activation of the NF-kappaB signaling pathway: A novel mechanism for aspirin-mediated apoptosis in colon cancer cells. FASEB J 15: 1273–1275, 2001

    Google Scholar 

  13. Spiegelman BM, Flier JS: Adipogenesis and obesity: Rounding out the big picture. Cell 87: 377–389, 1996

    Google Scholar 

  14. Van Bilsen M, Van der Vusse GJ, Gilde AJ, Lindhout M, Van der Lee KAJM: Peroxisome proliferator-activated receptors: Lipid binding proteins controlling gene expression. Mol Cell Biochem 239: 131–138, 2002

    Google Scholar 

  15. Delerive P, Fruchart JC, Staels B: Peroxisome proliferator-activated receptors in inflammation control. J Endocrinol 169: 453–459, 2001

    Google Scholar 

  16. Kersten S, Desvergne B, Wahli W: Roles of PPARs in health and disease. Nature 405: 421–424, 2000

    Google Scholar 

  17. He T-C, Chan TA, Vogelstein B, Kinzler KW: PPAδ is an APC-regulated target of nonsteroidal anti-inflammatory drugs. Cell 99: 335–345, 1999

    Google Scholar 

  18. Gupta RA, Tan J, Krause WF, Geraci MW, Willson TM, Dey SK, DuBois RN: Prostacyclin-mediated activation of peroxisome proliferator-activated receptor β in colorectal cancer. Proc Natl Acad Sci USA 97: 13275–13280, 2000

    Google Scholar 

  19. Tong BJ, Tan J, Tajeda L, Das SK, Chapman JA, DuBois RN, Dey SK: Heightened expression of cyclooxygenase-2 and peroxisome proliferator-activated receptor-delta in human endometrial adenocarcinoma. Neoplasia 2: 483–490, 2000

    Google Scholar 

  20. Hatae T, Wada M, Yokoyama C, Shimonishi M, Tanabe T: Prostacyclin-dependent apoptosis mediated by PPAR delta. J Biol Chem 276: 46260–46267, 2001

    Google Scholar 

  21. Kliewer SA, Forman BM, Blumberg B, Ong ES, Borgmeyer U, Mangelsdorf DJ, Umesono K, Evans RM: Differential expression and activation of a family of murine peroxisome proliferator-activated receptors. Proc Natl Acad Sci USA 91: 7355–7359, 1994

    Google Scholar 

  22. Schmidt A, Endo N, Rutledge SJ, Vogel R, Shinar D, Rodan GA: Identification of a new member of the steroid hormone receptor superfamily that is activated by a peroxisome proliferator and fatty acids. Mol Endocrinol 6: 1634–1641, 1992

    Google Scholar 

  23. Skogsberg J, Kannisto K, Roshani L, Gagne E, Hamsten A, Larsson C, Ehrenborg E: Characterization of the human peroxisome proliferator activated receptor delta gene and its expression. Int J Mol Med 6: 73–81, 2000

    Google Scholar 

  24. Kwon G, Hill JR, Corbett JA, McDaniel ML: Effects of aspirin on nitric oxide formation and de novo protein synthesis by RINm5F cells and rat islets. Mol Phamacol 52: 398–405, 1997

    Google Scholar 

  25. Iglesias-Serret D, Piqué M, Gil J, Pons G, López JM: Transcriptional and translational control of Mcl-1 during apoptosis. Arch Biochem Biophys 417: 141–152, 2003

    Google Scholar 

  26. Mascaró C, Acosta E, Ortiz JA, Marrero PF, Hegardt FG, Haro D: Control of human muscle-type carnitine palmitoyltransferase I gene tran-scription by peroxisome proliferator-activated receptor. J Biol Chem 273: 8560–8563, 1998

    Google Scholar 

  27. Forman BM, Chen J, Evans RM: Hypolipidemic drugs, polyunsaturated fatty acids, and eicosanoids are ligands for peroxisome proliferator-activated receptors alpha and delta. Proc Natl Acad Sci USA 94: 4312–4317, 1997

    Google Scholar 

  28. Suchanek KM, May FJ, Lee WJ, Holman NA, Roberts-Thomson SJ: Peroxisome proliferator-activated receptor β expression in human breast epithelial cell lines of tumorigenic and non-tumorigenic origin. Int J Biochem Cell Biol 34: 1051–1058, 2002

    Google Scholar 

  29. Lehmann JM, Lenhard JM, Oliver BB, Ringold GM, Kliewer SA: Peroxisome proliferator-activated receptors α and γ are activated by indomethacin and other non-steroidal anti-inflammatory drugs. J Biol Chem 272: 3406–3410, 1997

    Google Scholar 

  30. Park BH, Vogelstein B, Kinzler KW: Genetic disruption of PPAβ decreases the tumorigenicity of human colon cancer cells. Proc Natl Acad Sci USA 98: 2598–2603, 2001

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Unitat de Bioquímica, Departament de Ciències Fisiològiques II, Universitat de Barcelona, Campus de Bellvitge, E-08907, L'Hospitalet, Spain

    José M. López, Manuel A. Fernández, Maria Piqué & Joan Gil

  2. Centre de Regulació Genòmica, Programa d'Expressió Gènica, Pg. Maritim 37-49, 08003, Barcelona, Spain.

    José M. López & Maria Piqué

  3. Departament de Biologia Celular i Anatomia Patològica, Institut d' Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Facultat de Medicina, Universitat de Barcelona, 08036, Barcelona, Spain

    Manuel A. Fernández

Authors
  1. José M. López
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Manuel A. Fernández
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Maria Piqué
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Joan Gil
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

López, J.M., Fernández, M.A., Piqué, M. et al. Aspirin-induced apoptosis in Jurkat cells is not mediated by peroxisome proliferator-activated receptor delta. Mol Cell Biochem 266, 57–63 (2004). https://doi.org/10.1023/B:MCBI.0000049138.67699.7b

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/B:MCBI.0000049138.67699.7b

Search

Navigation