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[Study on the mechanisms of telomerase regulations during apoptosis of the human MDS-RAEB cell line MUTZ-1 cells induced by arsenic trioxide].
- Source :
-
Zhongguo shi yan xue ye xue za zhi [Zhongguo Shi Yan Xue Ye Xue Za Zhi] 2005 Aug; Vol. 13 (4), pp. 615-9. - Publication Year :
- 2005
-
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).
- Subjects :
- Antineoplastic Agents pharmacology
Arsenic Trioxide
Cell Line
Dose-Response Relationship, Drug
Flow Cytometry
Gene Expression drug effects
Humans
Myelodysplastic Syndromes genetics
Myelodysplastic Syndromes metabolism
Myelodysplastic Syndromes pathology
Proto-Oncogene Proteins c-bcl-2 genetics
RNA, Messenger genetics
RNA, Messenger metabolism
Reverse Transcriptase Polymerase Chain Reaction
Telomerase metabolism
Telomeric Repeat Binding Protein 2 genetics
bcl-2-Associated X Protein genetics
Apoptosis drug effects
Arsenicals pharmacology
Oxides pharmacology
Telomerase genetics
Subjects
Details
- Language :
- Chinese
- ISSN :
- 1009-2137
- Volume :
- 13
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Zhongguo shi yan xue ye xue za zhi
- Publication Type :
- Academic Journal
- Accession number :
- 16129045