RESEARCH ARTICLE


Downregulation of Telomerase in CoCl2-Induced Apoptosis of Myeloid Leukemic Cells



Ya-Bei Xua, Jing Zhangb, Evelyne Segal- Bendirdjianc, Ying-Li Wu a, *, Guo-Qiang Chen a, b, *
a The Dept. of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China
b Institute of Health Science, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China
c INSERM U685, Institut d'Hématologie, Hôpital Saint-Louis, 1 avenue Claude Vellefaux, 75010 Paris, France


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© 2008 Xu et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Dept. of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao-Tong University School of Medicine, No. 280, Chong-Qing South Road, Shanghai 200025, China; Tel/Fax: 86-21- 64154900; E-mail: chengq@shsmu.edu.cn or wuyingli@shsmu.edu.cn


Abstract

Many reports showed that hypoxia-inducible factor-1α (HIF-1α), the main factor activated by hypoxia, plays a role in the transcriptional regulation of the human telomerase reverse transcriptase (hTERT), one of the critical elements of the oncogenic process. As a hypoxia-mimetic agent, cobalt chloride (CoCl2) can induce the accumulation of HIF-1α. Herein, we demonstrated that hTERT expression was greatly decreased during CoCl2-induced apoptosis in leukemic cell lines while overexpression of hTERT inhibited CoCl2-induced apoptosis. Knockdown of HIF-1α by shRNA in U937 cells did not abrogate CoCl2-induced hTERT downregulation nor CoCl2-induced apoptosis while inducible expression of HIF- 1α decreased the expression of hTERT. Furthermore, CoCl2 could decrease the c-myc protein in all the cells tested, no matter the HIF-1α was silenced or not. Taken together, we demonstrated that downregulation of hTERT contributes to CoCl2-induced apoptosis in leukemic cell lines and HIF-1α is not indispensable for CoCl2 induced downregulation of hTERT.

Keywords: Telomerase, Apoptosis, CoCl2, HIF-1α, Leukemia.