Study on the mechanisms of telomerase regulations during apoptosis of the human MDS-RAEB cell line MUTZ-1 cells induced by arsenic trioxide.
- Author:
Hong-Yan TONG
1
;
Jie JIN
;
Wei-Lai XU
;
Wen-Bin QIAN
;
Mao-Fang LIN
Author Information
1. Department of Hematology, The First Affiliated Hospital, Medical College, Zhejiang University, Hangzhou 310003, China. hongyantong@yahoo.com.cn
- Publication Type:Journal Article
- MeSH:
Antineoplastic Agents;
pharmacology;
Apoptosis;
drug effects;
Arsenicals;
pharmacology;
Cell Line;
Dose-Response Relationship, Drug;
Flow Cytometry;
Gene Expression;
drug effects;
Humans;
Myelodysplastic Syndromes;
genetics;
metabolism;
pathology;
Oxides;
pharmacology;
Proto-Oncogene Proteins c-bcl-2;
genetics;
RNA, Messenger;
genetics;
metabolism;
Reverse Transcriptase Polymerase Chain Reaction;
Telomerase;
genetics;
metabolism;
Telomeric Repeat Binding Protein 2;
genetics;
bcl-2-Associated X Protein;
genetics
- From:
Journal of Experimental Hematology
2005;13(4):615-619
- CountryChina
- Language: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).
