[Study on the mechanisms of telomerase regulations during apoptosis of the human MDS-RAEB cell line MUTZ-1 cells induced by arsenic trioxide]

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2005 Aug;13(4):615-9.
[Article in Chinese]

Abstract

To investigate the mechanisms of the telomerase regulations during the apoptosis of the human MDS-RAEB cell line MUTZ-1 cells induced by arsenic trioxide (As(2)O(3)), telomerase activity was detected by TRAP-ELISA and the expressions of mRNAs of hTERT, TRF1 (TTAGGG repeat binding factor 1), TRF2 (TTAGGG repeat binding factor 2), bcl-2, and bax genes were detected by RT-PCR. Apoptosis was detected by translocation of phosphatidylserine (PS) by flow cytometry. The results showed that 1 - 8 micromol/L of As(2)O(3) induced typical apoptosis of MUIZ-1 cells in the dose-and time-dependent manners, the telomerase activity could be down-regulated at this concentration and negatively correlated with increased apoptosis (r = -0.938, P = 0.018). The expression of telomerase activity was positively related to the expression of hTERT (r = 0.783, P = 0.022), but As(2)O(3) had no effect on the mRNA expression of TRF1 and TRF2 genes. The inhibition of telomerase activity by As(2)O(3) on MUTZ-1 cells was accompanied with the low expression of bcl-2 gene and the decrease of bcl-2/bax ratio. It is concluded that the apoptosis of MUTZ-1cells induced by As(2)O(3) may occur via the inhibition of telomerase activity and down-regulation of the expression of hTERT mRNA, and this may be one of the mechanisms inducing apoptosis in MUTZ-1 cells treated by As(2)O(3).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects*
  • Arsenic Trioxide
  • Arsenicals / pharmacology*
  • Cell Line
  • Dose-Response Relationship, Drug
  • Flow Cytometry
  • Gene Expression / drug effects
  • Humans
  • Myelodysplastic Syndromes / genetics
  • Myelodysplastic Syndromes / metabolism
  • Myelodysplastic Syndromes / pathology
  • Oxides / pharmacology*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Telomerase / genetics*
  • Telomerase / metabolism
  • Telomeric Repeat Binding Protein 2 / genetics
  • bcl-2-Associated X Protein / genetics

Substances

  • Antineoplastic Agents
  • Arsenicals
  • BAX protein, human
  • Oxides
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • TERF2 protein, human
  • Telomeric Repeat Binding Protein 2
  • bcl-2-Associated X Protein
  • Telomerase
  • Arsenic Trioxide