Skip to main content
SpringerLink
Log in

Short interfering RNA against the PDCD5 attenuates cell apoptosis and caspase-3 activity induced by Bax overexpression

  • Published:
Apoptosis Aims and scope Submit manuscript

Abstract

The programmed cell death 5 (PDCD5) protein plays an important apoptosis-accelerating role in cells undergoing apoptosis. Decreased expression of PDCD5 has been detected in various human carcinomas. Here we describe that one potent short interfering RNA (siRNA) against the PDCD5 (siPDCD5) specifically inhibits the expression of PDCD5 at both the mRNA and protein level. Cells with decreased PDCD5 expression displayed reduced sensitivity to an apoptotic stimulus induced by Bax overexpression in HeLa, HEK293 and 293T cell lines. Furthermore, we also show that siPDCD5 inhibited both caspase-3 activity and procaspase-3 cleavage. Suppressed expression of PDCD5 attenuates the release of cytochrome c from mitochondria to cytosol induced by Bax overexpression. This phenomenon is accompanied by the reduced translocation of Bax from the cytosol to mitochondria. MTT assay shows that targeted suppression of PDCD5 expression markedly promoted cell proliferation in Hela and HEK293 cell lines. Our data suggests that PDCD5 may exert its effects through pathway of mitochondria by modulating Bax translocation, cytochrome c release and caspase 3 activation directly or indirectly, and that decreased PDCD5 expression may be one of the mechanisms by which tumor cells achieve resistance to apoptotic stimulus induced by anticancer drugs.

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. Reed JC. Dysregulation of apoptosis in cancer. Cancer J Sci Am 1998; Suppl 1: S8–14.

    Google Scholar 

  2. Shimohama S. Apoptosis in Alzheimer's disease-an update. Apoptosis 2000; 5: 9–16.

    Article  CAS  PubMed  Google Scholar 

  3. Yuan J, Yankner BA. Apoptosis in the nervous system.Nature 2000; 407: 802–809.

    Article  CAS  PubMed  Google Scholar 

  4. Grütter MG. Caspases: key players in programmed cell death. Curr Opin Struct Biol 2000; 10: 649–655.

    Article  PubMed  Google Scholar 

  5. Stennicke HR, Salvesen GS. Caspases-controlling intracellular signals by protease zymogen activation.Biochim Biophys Acta 2000; 1477: 299–306.

    CAS  PubMed  Google Scholar 

  6. Antonsson B, Martinou JC. The Bcl-2 protein family. Exp Cell Res 2000; 256: 50–57.

    CAS  Google Scholar 

  7. Song Z, Steller H. Death by design: mechanism and control of apoptosis. Trends Cell Biol 1999; 9: M49–52.

    Article  CAS  PubMed  Google Scholar 

  8. Deng YB, Lin YH, Wu XW. TRAIL-induced apoptosis requires Bax-dependent mitochondrial release of Smac/DIABLO.Genes Dev 2002; 16: 33–45.

    CAS  Google Scholar 

  9. Deveraux QL, Reed JC. IAP family proteins-suppressors of apoptosis.Genes Dev 1999; 13: 239–252.

    CAS  PubMed  Google Scholar 

  10. Tsujimoto Y, Shimizu S. Bcl-2 family: Life-or-death switch. FEBS Lett 2000; 466: 6–10.

    Article  CAS  PubMed  Google Scholar 

  11. Liu HT, Wang YG, Ma DL, et al. TFAR19, a novel apoptosis-related gene cloned from human leukemia cell line TF-1, could enhance apoptosis of some tumor cells induced by growth factor withdrawal.Biochem Biophys Res Commun 1999; 254: 203–210.

    CAS  PubMed  Google Scholar 

  12. Dobson AT, Raja R, Abeyta MJ, Taylor T, Shen S, Pera RA. The unique transcriptome through day 3 of human preimplantation development.Hum Mol Genet 2004; 13(14): 1461–1470.

    CAS  Google Scholar 

  13. Chen YY, Sun RH, Ma DL, et al. Nuclear translocation of PDCD5 (TFAR19): An early signal for apoptosis?.FEBS lett 2001; 509: 191–196.

    CAS  PubMed  Google Scholar 

  14. Wang Y, Li XT, Ma DL, et al. An alternative form of paraptosis-like cell death, triggered by TAJ/TROY and enhanced by PDCD5 overexpression.J Cell Sci 2004; 117: 1525–1532.

    CAS  PubMed  Google Scholar 

  15. Rui M, Chen YY, Zhang YM, Ma DL. Transfer of anti-TFAR19 monoclonal antibody into HeLa cells by in situ electroporation can inhibit the apoptosis.Life Sci 2002; 71: 1771–1778.

    Article  CAS  PubMed  Google Scholar 

  16. Xu XR, Huang J, Xu ZG, et al. Insight into hepatocellular carcinogenesis at transcriptome level by comparing gene expression profiles of hepatocellular carcinoma with those of corresponding noncancerous liver.Proc Natl Acad Sci USA 2001; 98(26): 15089–15094.

    Article  CAS  PubMed  Google Scholar 

  17. Hedenfalk I, Duggan D, Chen Y, et al. Gene-expression profiles in hereditary breast cancer. N Engl J Med 2001; 344: 539–548.

    CAS  Google Scholar 

  18. Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells.Nature 2001; 411: 494–498.

    Article  CAS  PubMed  Google Scholar 

  19. caplen NJ, Parrish S, Imani F, Fire A, Morgen RA. Specific inhibition of gene expression by small double-stranded RNAs in invertebrate and vertebrate systems.Proc Natl Acad Sci USA 2001; 98(17): 9742–9747.

    Article  CAS  PubMed  Google Scholar 

  20. Singer O, Yanai A, Verma IM. Silence of the gene.Proc Natl Acad Sci USA 2004; 101(15): 5313–5314.

    Article  CAS  PubMed  Google Scholar 

  21. Gupta S, Schoer RA, Egan JE, Hannon GJ, Mittal V. Inducible, reversible, and stable RNA interference in mammalian cells.Proc Natl Acad Sci USA 2004; 101(7): 1927–1932.

    Article  CAS  PubMed  Google Scholar 

  22. Bertrand JR, Pottier M, Vekris A, Opolon P, Maksimenko A, Malvy C. Comparison of antisense oligonucleotides and siRNAs in cell culture and in vivo.Biochem Biophys Res Commun 2002; 296: 1000–1004.

    Article  CAS  Google Scholar 

  23. Gitlin L, Karelsky S, Andino R. Short interfering RNA confers intracellular antiviral immunity in human cells.Nature 2002; 418: 430–434.

    Article  CAS  PubMed  Google Scholar 

  24. Tompkins SM, Lo CY, Tumpey TM, Epstein SL. Protection against lethal influenza virus challenge by RNA interference in vivo.Proc Natl Acad Sci USA 2004; 101(23): 8682–8686.

    Article  CAS  PubMed  Google Scholar 

  25. Nagy P, Arndt-Jovin DJ, Jovin TM. Small interfering RNAs suppress the expression of endogenous and GFP-fused epidermal growth factor receptor (erbB1) and induce apoptosis in erbB1-overexpressing cells.Exp Cell Res 2003; 285: 39–49.

    Article  CAS  PubMed  Google Scholar 

  26. Wall NR, Shi Y. Small RNA: can RNA interference be exploited for therapy?Lancet 2003; 362: 1401–1403.

    Article  CAS  PubMed  Google Scholar 

  27. Dorsett Y, Tuschl T. SiRNA: applications in functional genomics and potential as therapeutics.Nat Rev Drug Discov 2004; 3: 318–329.

    Article  CAS  PubMed  Google Scholar 

  28. Fadok VA, Bratton DL, Frasch SC, Warner ML, Henson PM. The role of phosphatidylserine in recognition of apoptotic cells by phagocytes.Cell Death Differ 1998; 5: 551–562.

    Article  CAS  PubMed  Google Scholar 

  29. Smith JD, Waelde C, Horwitz A, Zheng P. Evaluation of the role of phosphatidylserine translocase activity in ABCA1-mediated lipid efflux.J Biol Chem 2002; 277(20): 17797–17803.

    CAS  PubMed  Google Scholar 

  30. Tian HK, Xla T, Jiang CS, Zhang HM, Wang K, Li XJ. TFAR19 enhances the opening of permeability transition pore in the mitochondria membrane of mice liver.Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao (Shanghai) 2002; 34(3): 279–284. Chinese.

    CAS  Google Scholar 

  31. Li L, Chen YY, Zheng R, Ma DL, Wang DB. Expression of TFAR19 in apoptotic processes of Jurkat cells induced with various methods.Zhong Guo Shi Yan Xue Ye Xue Za Zhi 2000; 8(2): 81–84. Chinese.

    Google Scholar 

  32. Abraham MC, Shaham S. Death without caspases,caspases without death.Trends Cell Biol 2004; 14(4): 184–193.

    Article  CAS  PubMed  Google Scholar 

  33. Earnshaw WC, Martins LM, Kaufmann SH. Mammalian caspases: structure, activation, substrates and functions during apoptosis.Annu Rev Biochem 1999; 68: 383–424.

    Article  CAS  PubMed  Google Scholar 

  34. Meier P, Finch A, Evan G. Apoptosis in development.Nature 2000; 407: 796–801.

    Article  CAS  PubMed  Google Scholar 

  35. Yuan J, Yankner BA. Apoptosis in the nervous system.Nature 2000; 407: 802–809.

    Article  CAS  PubMed  Google Scholar 

  36. Ji X, Cheung R, Cooper S, Li Q, Greenberg HB, He XS. Interferon alfa regulated gene expression in patients initiating interferon treatment for chronic hepatitis C. Hepatology 2003; 37(3): 610–621. Erratum in: Hepatology 2003; 37(6): 1503.

    Article  CAS  PubMed  Google Scholar 

  37. Cecconi D, Scarpa A, Donadelli M, et al. Proteomic profiling of pancreatic ductal carcinoma cell lines treated with trichostatin-A.Electrophoresis 2003; 24(11): 1871–1878.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Medical Immunology, School of Basic Medical Science, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100083, People's Republic of China

    L. N. Chen & Y. Wang

  2. Center for Human Disease Genomics, Peking University, 38 Xueyuan Road, Beijing, 100083, People's Republic of China

    D. L. Ma & Y. Y. Chen

Authors
  1. L. N. Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Y. Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D. L. Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Y. Y. Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Y. Y. Chen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chen, L.N., Wang, Y., Ma, D.L. et al. Short interfering RNA against the PDCD5 attenuates cell apoptosis and caspase-3 activity induced by Bax overexpression. Apoptosis 11, 101–111 (2006). https://doi.org/10.1007/s10495-005-3134-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10495-005-3134-y

Keywords

Search

Navigation