The Open Hematology Journal

2008, 2 : 74-80
Published online 2008 May 20. DOI: 10.2174/1874276900802010074
Publisher ID: TOHJ-2-74

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

Ya-Bei Xu , Jing Zhang , Evelyne Segal- Bendirdjian , Ying-Li Wu and Guo-Qiang Chen
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.

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.