Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Scientific Correspondence
  • Published:

Clozapine inhibits cell survival-related genes in bone marrow cells

Molecular Psychiatry volume 9, pages 545–546 (2004)Cite this article

SIR — Clozapine, an atypical antipsychotic agent, has been proven to be effective in the treatment of refractory schizophrenia.1 As the idiosyncratic clozapine-induced agranulocytosis occurs in 0.5–2% of the treated patients, the use of clozapine has been limited.1 Patients should monitor their white blood cell count during the treatment period.2 The mechanism of clozapine-induced agranulocytosis is not fully explained; however, it has been postulated as immune-mediated mechanism and direct toxic effects.3,4 It has been demonstrated that the reactive nitrenium ion, a toxic metabolite, is produced from clozapine through myeloperoxidase-H2O2-dependent reaction, and then induces the apoptosis of neutrophils in vitro.4

In order to determine whether clozapine-treated bone marrow cells were susceptible to cell death, we compared the expression profiles of bone marrow cells between clozapine- and vehicle (saline)-treated mice using cDNA microarray analysis. Clozapine (10 mg/kg, i.p.) was injected to male C57BL/6 mice (n=5) for 2 weeks. The peripheral bloods in orbital venous plexus were sampled to count neutrophils, and bone marrow cells were collected from femurs and tibias. Total RNA was isolated immediately, and analysis of 7.4K Mice cDNA microarray (DigitalGenomics, Seoul, ROK) was performed according to the previous procedure.5 The cDNA microarray analysis was repeated twice. The global M method was used in this study to normalize intensity ratio of each gene expression. The expression level of selected genes was confirmed by RT-PCR using Gapdh as internal standard.5

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

References

  1. Baldessarini RJ et al. N Engl J Med 1991; 324: 746–754.

    Article  Google Scholar 

  2. Atkin K et al. Br J Psychiatry 1996; 169: 483–488.

    Article  CAS  Google Scholar 

  3. Uetrecht JP . Drug Saf 1992; 7: 52–56.

  4. Williams DP et al. Mol Pharmacol 2000; 58: 207–216.

    Article  CAS  Google Scholar 

  5. Mu X et al. Nucl Acids Res 2001; 29: 4983–4993.

  6. Jaffer ZM, Chernoff J . Int J Biochem Cell Biol 2002; 34: 713–717.

  7. Schürmann A et al. Mol Cell Biol 2000; 20: 453–461.

  8. Datta SR et al. Cell 1997; 91: 231–241.

    Article  CAS  Google Scholar 

  9. Nishida K, Kaziro Y, Satoh T . Oncogene 1999; 18: 407–415.

    Article  CAS  Google Scholar 

  10. Yano S, Tokumitsu H, Soderling R . Nature 1998; 396: 584–587.

    Article  CAS  Google Scholar 

  11. McKay MJ et al. Genomics 1996; 36: 305–315.

    Article  CAS  Google Scholar 

  12. Kim MS et al. Biochem Biophys Res Commun 2001; 281: 1106–1112.

Download references

Acknowledgements

This work was supported by a grant of the Biomedical Brain Research Center Grant, Ministry of Health and Welfare, Republic of Korea (01-PJ8-PG6-01NE01-0003).

Author information

Authors and Affiliations

  1. Department of Pharmacology, Kohwang Medical Research Institute, College of Medicine, Kyung Hee University, Seoul, Korea

    H J Lee, S Y Jin, M S Hong, H J Park, S V Yim, J W Kim, H K Park & J H Chung

  2. Seoul National Mental Hospital, Seoul, Korea

    M K Kim

  3. Department of Pharmacology, College of Medicine, Kangwon National University, Kangwon, Korea

    S S Kim

Authors
  1. H J Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S Y Jin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M S Hong
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H J Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M K Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. S V Yim
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. J W Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. H K Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. S S Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. J H Chung
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J H Chung.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lee, H., Jin, S., Hong, M. et al. Clozapine inhibits cell survival-related genes in bone marrow cells. Mol Psychiatry 9, 545–546 (2004). https://doi.org/10.1038/sj.mp.4001489

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.mp.4001489

Search

Advanced search

Quick links