Telomerase-dependent reactivation of DNA synthesis in macrophages implies alteration of telomeres

Y. E. Yegorov, E. V. Kazimirchuk, S. M. Terekhov, D. N. Karachentsev, E. A. Shirokova, A. L. Khandazhinskaya, J. A. Meshcheryakova, D. R. Corey, A. V. Zelenin

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

In previous work we demonstrated that various types of cultured cells with a limited life span could not reactivate DNA synthesis in the nuclei of mouse peritoneal macrophages in heterokaryons. We now investigate the role of telomerase in the process of the macrophage nucleus reactivation in heterokaryons with immortal telomerase-positive 3T3 Swiss mouse fibroblasts and human fibroblasts with introduced hTERT gene. We report that introduction of the hTERT gene into human diploid fibroblasts results in emergence of telomerase activity in these cells and the ability to induce the reactivation of DNA synthesis in the macrophage nuclei in heterokaryons. Inhibition of telomerase activity in heterokaryons by reverse transcriptase inhibitors (azidothymidine and guanosine polyphosphonate analogues) and by a 2′-O-methyl-RNA oligonucleotide anti-sense to the template region of telomerase RNA, block reactivation of DNA synthesis in macrophage nuclei without inhibiting DNA synthesis in the nuclei of fibroblasts. Our results suggest alterations (shortening or damage) in the macrophage telomere structure. As far as we know, heterokaryons with macrophages are the first cellular model for rapid investigation of the effects of telomerase inhibitors.

Original languageEnglish (US)
Pages (from-to)1019-1027
Number of pages9
JournalCell Biology International
Volume26
Issue number12
DOIs
StatePublished - Jan 1 2002

Keywords

  • Differentiation
  • Heterokaryons
  • Human fibroblasts
  • Macrophages
  • Proliferation
  • Telomerase
  • Telomerase inhibition
  • Telomeres

ASJC Scopus subject areas

  • Cell Biology

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    Yegorov, Y. E., Kazimirchuk, E. V., Terekhov, S. M., Karachentsev, D. N., Shirokova, E. A., Khandazhinskaya, A. L., Meshcheryakova, J. A., Corey, D. R., & Zelenin, A. V. (2002). Telomerase-dependent reactivation of DNA synthesis in macrophages implies alteration of telomeres. Cell Biology International, 26(12), 1019-1027. https://doi.org/10.1006/cbir.2002.0961