Skip to main content
SpringerLink
Log in

Histone H4 deacetylation down-regulates catalase gene expression in doxorubicin-resistant AML subline

  • Original Research
  • Published:
Cell Biology and Toxicology Aims and scope Submit manuscript

Abstract

We explored if epigenetic mechanisms could be involved in the down-regulated expression of catalase gene (CAT) in the doxorubicin-resistant acute myelogenous leukemia (AML)-2/DX100 cells. Down-regulated CAT expression in AML-2/DX100 cells was completely recovered after treatment of hydrogen peroxide (H2O2) and histone deacetylase inhibitor, trichostatin A (TSA) but was increased slightly by the treatment of DNA methylation inhibitor, 5-aza-2′-deoxycytidine (5-AdC). Bisulfite-sequencing PCR revealed that a CpG island of CAT was not methylated in AML-2/DX100 cells. Chromatin immunoprecipitation assay confirmed that acetylation of histone H4 in AML-2/DX100 cells significantly decreased as compared with that in AML-2/WT cells, which was significantly increased by TSA more than 5-AdC. Meanwhile, overexpression of other up-regulated peroxidase genes appears to make compensation for decreased H2O2-scavenging activity for the down-regulated CAT expression in AML-2/DX100 cells. These results suggest that histone H4 deacetylation is responsible for the down-regulated CAT expression in AML-2/DX100 cells, which are well adapted to oxidative stress.

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

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Choi CH, Kim HS, Rha HS, Jeong JH, Park YH, Min YD, et al. Drug concentration-dependent expression of multidrug resistance-associated protein and P-glycoprotein in the doxorubicin-resistant acute myelogenous leukemia sublines. Mol Cells. 1999;9:314–9.

    PubMed  CAS  Google Scholar 

  • Clare DA, Duong MN, Darr D, Archibald F, Fridovich I. Effects of molecular oxygen on detection of superoxide radical with nitroblue tetrazolium and on activity stains for catalase. Anal Biochem. 1984;140:532–7.

    Article  PubMed  CAS  Google Scholar 

  • Crescimanno M, D’Alessandro N, Armata MG, Toulmond S, Tapiero H. Modulation of the antioxidant activities in dox-sensitive and -resistant Friend leukemia cells. Effect of doxorubicin. Anticancer Res. 1991;11:901–3.

    PubMed  CAS  Google Scholar 

  • Egger G, Aparicio AM, Escobar SG, Jones PA. Inhibition of histone deacetylation does not block resilencing of p16 after 5-aza-2′-deoxycytidine treatment. Cancer Res. 2007;67:346–53.

    Article  PubMed  CAS  Google Scholar 

  • Felsenfeld G, Groudine M. Controlling the double helix. Nature. 2003;421:448–53.

    Article  PubMed  Google Scholar 

  • Fischle W, Wang Y, Allis CD. Histone and chromatin cross-talk. Curr Opin Cell Biol. 2003;15:172–83.

    Article  PubMed  CAS  Google Scholar 

  • Fuks F, Hurd PJ, Wolf D, Nan X, Bird AP, Kouzarides T. The methyl-CpG-binding protein MeCP2 links DNA methylation to histone methylation. J Biol Chem. 2003;278:4035–40.

    Article  PubMed  CAS  Google Scholar 

  • Geiman TM, Robertson KD. Chromatin remodeling, histone modifications, and DNA methylation-how does it all fit together? J Cell Biochem. 2002;87:117–25.

    Article  PubMed  CAS  Google Scholar 

  • Hampsey M. Molecular genetics of the RNA polymerase II general transcriptional machinery. Microbiol Mol Biol Rev. 1998;62:465–503.

    PubMed  CAS  Google Scholar 

  • Harris RN, Doroshow JH. Effect of doxorubicin-enhanced hydrogen peroxide and hydroxyl radical formation on calcium sequestration by cardiac sarcoplasmic reticulum. Biochem Biophys Res Commun. 1985;130:739–45.

    Article  PubMed  CAS  Google Scholar 

  • Hoffschir F, Vuillaume M, Sabatier L, Ricoul M, Daya-Grosjean L, Estrade S, et al. Decrease in catalase activity and loss of the 11p chromosome arm in the course of SV40 transformation of human fibroblasts. Carcinogenesis. 1993;14:1569–72.

    Article  PubMed  CAS  Google Scholar 

  • Ikeda M, Kodama H, Fukuda J, Shimizu Y, Murata M, Kumagai J, et al. Role of radical oxygen species in rat testicular germ cell apoptosis induced by heat stress. Biol Reprod. 1999;61:393–9.

    Article  PubMed  CAS  Google Scholar 

  • Ito K, Hanazawa T, Tomita K, Barnes PJ, Adcock IM. Oxidative stress reduces histone deacetylase 2 activity and enhances IL-8 gene expression: role of tyrosine nitration. Biochem Biophys Res Commun. 2004;315:240–5.

    Article  PubMed  CAS  Google Scholar 

  • Jones PL, Veenstra GJ, Wade PA, Vermaak D, Kass SU, Landsberger N, et al. Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription. Nat Genet. 1998;19:187–91.

    Article  PubMed  CAS  Google Scholar 

  • Kang YJ, Chen Y, Epstein PN. Suppression of doxorubicin cardiotoxicity by overexpression of catalase in the heart of transgenic mice. J Biol Chem. 1996;271:12610–6.

    Article  PubMed  CAS  Google Scholar 

  • Kang J, Chen J, Shi Y, Jia J, Zhang Y. Curcumin-induced histone hypoacetylation: the role of reactive oxygen species. Biochem Pharmacol. 2005;69:1205–13.

    Article  PubMed  CAS  Google Scholar 

  • Kim HS, Lee TB, Choi CH. Down-regulation of catalase gene expression in the doxorubicin-resistant AML subline AML-2/DX100. Biochem Biophys Res Commun. 2001a;281:109–14.

    Article  CAS  Google Scholar 

  • Kim HS, Min YD, Choi CH. Double-edged sword of chemosensitizer: increase of multidrug resistance protein (MRP) in leukemic cells by an MRP inhibitor probenecid. Biochem Biophys Res Commun. 2001b;283:64–71.

    Article  CAS  Google Scholar 

  • Laird PW. Cancer epigenetics. Hum Mol Genet. 2005;14(Spec No 1):R65–76.

    Article  PubMed  CAS  Google Scholar 

  • Li LC, Dahiya R. MethPrimer: designing primers for methylation PCRs. Bioinformatics (Oxford). 2002;18:1427–31.

    Article  CAS  Google Scholar 

  • Li ZX, Ma X, Wang ZH. A differentially methylated region of the DAZ1 gene in spermatic and somatic cells. Asian J Androl. 2006;8:61–7.

    Article  PubMed  CAS  Google Scholar 

  • Lin C, Kang J, Zheng R. Vitamin K3 triggers human leukemia cell death through hydrogen peroxide generation and histone hyperacetylation. Pharmazie. 2005;60:765–71.

    PubMed  CAS  Google Scholar 

  • Lu J, Papp LV, Fang J, Rodriguez-Nieto S, Zhivotovsky B, Holmgren A. Inhibition of mammalian thioredoxin reductase by some flavonoids: implications for myricetin and quercetin anticancer activity. Cancer Res. 2006;66:4410–8.

    Article  PubMed  CAS  Google Scholar 

  • Matecic M, Stuart S, Holmes SG. SIR2-induced inviability is suppressed by histone H4 overexpression. Genetics. 2002;162:973–6.

    PubMed  CAS  Google Scholar 

  • Nakagawa CW, Yamada K, Mutoh N. Two distinct upstream regions are involved in expression of the catalase gene in Schizosaccharomyces pombe in response to oxidative stress. J Biochem (Tokyo). 1998;123:1048–54.

    CAS  Google Scholar 

  • Nakagawa CW, Yamada K, Mutoh N. Identification of the catalase gene promoter region involved in superinduction in Schizosaccharomyces pombe caused by cycloheximide and hydrogen peroxide. FEMS Microbiol Lett. 1999;173:373–8.

    Article  PubMed  CAS  Google Scholar 

  • Nonn L, Berggren M, Powis G. Increased expression of mitochondrial peroxiredoxin-3 (thioredoxin peroxidase-2) protects cancer cells against hypoxia and drug-induced hydrogen peroxide-dependent apoptosis. Mol Cancer Res. 2003;1:682–9.

    PubMed  CAS  Google Scholar 

  • Oh YK, Lee TB, Choi CH. Anti-oxidant adaptation in the AML cells supersensitive to hydrogen peroxide. Biochem Biophys Res Commun. 2004;319:41–5.

    Article  PubMed  CAS  Google Scholar 

  • Prahalathan C, Selvakumar E, Varalakshmi P. Remedial effect of dl-alpha-lipoic acid against adriamycin induced testicular lipid peroxidation. Mol Cell Biochem. 2004;267:209–14.

    Article  PubMed  CAS  Google Scholar 

  • Ramu A, Cohen L, Glaubiger D. Oxygen radical detoxification enzymes in doxorubicin-sensitive and -resistant P388 murine leukemia cells. Cancer Res. 1984;44:1976–80.

    PubMed  CAS  Google Scholar 

  • Santos-Rosa H, Schneider R, Bannister AJ, Sherriff J, Bernstein BE, Emre NC, et al. Active genes are tri-methylated at K4 of histone H3. Nature. 2002;419:407–11.

    Article  PubMed  CAS  Google Scholar 

  • Sato K, Ito K, Kohara H, Yamaguchi Y, Adachi K, Endo H. Negative regulation of catalase gene expression in hepatoma cells. Mol Cell Biol. 1992;12:2525–33.

    PubMed  CAS  Google Scholar 

  • Sun Y, Colburn NH, Oberley LW. Depression of catalase gene expression after immortalization and transformation of mouse liver cells. Carcinogenesis. 1993;14:1505–10.

    Article  PubMed  CAS  Google Scholar 

  • Thaete C, Brett D, Monaghan P, Whitehouse S, Rennie G, Rayner E, et al. Functional domains of the SYT and SYT-SSX synovial sarcoma translocation proteins and co-localization with the SNF protein BRM in the nucleus. Hum Mol Genet. 1999;8:585–91.

    Article  PubMed  CAS  Google Scholar 

  • Towbin H, Staehelin T, Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci USA. 1979;76:4350–4.

    Article  PubMed  CAS  Google Scholar 

  • Wada H, Kagoshima M, Ito K, Barnes PJ, Adcock IM. 5-Azacytidine suppresses RNA polymerase II recruitment to the SLPI gene. Biochem Biophys Res Commun. 2005;331:93–9.

    Article  PubMed  CAS  Google Scholar 

  • Yamaguchi Y, Sato K, Endo H. Depression of catalase gene expression in the liver of tumor bearing nude mice. Biochem Biophys Res Commun. 1992;189:1084–9.

    Article  PubMed  CAS  Google Scholar 

  • Yoshida M, Kijima M, Akita M, Beppu T. Potent and specific inhibition of mammalian histone deacetylase both in vivo and in vitro by trichostatin A. J Biol Chem. 1990;265:17174–9.

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by National Research Foundation of Korea grant funded by the Ministry of Education, Science and Technology (MEST) through the Research Center for Resistant Cells (R13-2003-009). We thank Mrs. H. S. Kim and Y. K. Seo for expert technical assistance.

Author information

Authors and Affiliations

  1. Research Center for Resistant Cells, Chosun University Medical School, Chosun University, Gwangju, 501-759, Republic of Korea

    Tae-Bum Lee, Young-Sook Moon & Cheol-Hee Choi

  2. Department of Pharmacology, Chosun University Medical School, Chosun University, Gwangju, 501-759, Republic of Korea

    Cheol-Hee Choi

Authors
  1. Tae-Bum Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Young-Sook Moon
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Cheol-Hee Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Cheol-Hee Choi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lee, TB., Moon, YS. & Choi, CH. Histone H4 deacetylation down-regulates catalase gene expression in doxorubicin-resistant AML subline. Cell Biol Toxicol 28, 11–18 (2012). https://doi.org/10.1007/s10565-011-9201-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10565-011-9201-y

Keywords

Search

Navigation