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Blood, 1 November 2005, Vol. 106, No. 9, pp. 3200-3205. Prepublished online as a Blood First Edition Paper on July 14, 2005; DOI 10.1182/blood-2005-04-1386. This Article Full Text (PDF) All Versions of this Article: 2005-04-1386v1 106/9/3200    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Beyne-Rauzy, O. Articles by Mansat- De Mas, V. Search for Related Content PubMed PubMed Citation Articles by Beyne-Rauzy, O. Articles by Mansat- De Mas, V. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 5, 2005 Accepted June 30, 2005 Tumor necrosis factor alpha inhibits hTERT gene expression in human myeloid normal and leukemic cells Odile Beyne-Rauzy, Nais Prade-Houdellier, Cecile Demur, Christian Recher, Jacques Ayel, Guy Laurent, and Veronique Mansat- De Mas* INSERM U563, CHU Purpan, Toulouse, France; Service de Medecine Interne, CHU Purpan, Toulouse, France INSERM U563, CHU Purpan, Toulouse, France INSERM U563, CHU Purpan, Toulouse, France; Laboratoire d'Hematologie Biologique, CHU Purpan, Toulouse, France INSERM U563, CHU Purpan, Toulouse, France; Service d'Hematologie, CHU Purpan, Toulouse, France Service d'Orthopedie, CHU Purpan, Toulouse, France * Corresponding author; email: demas.v{at}chu-toulouse.fr. Telomerase catalytic subunit (hTERT) has been shown to play a critical role not only in telomere homeostasis but also in cellular survival, DNA repair, and genetic stability. In a previous study, we described that TNF induced in the leukemic KG1 cells a senescence state characterized by decreased hTERT activity followed by prolonged growth arrest, increased -galactosidase activity, telomere shortening and major chromosomal instability. Interestingly, GM-CSF abrogated all these events. In the present study, we show for the first time that TNF acts by inhibiting hTERT gene in both normal CD34+ cells and fresh leukemic cells. Using KG1 cells as a representative cellular model, we show that TNF induced sphingomyelin hydrolysis, ceramide production and JNK activation all of which are critical components of TNF signaling resulting in hTERT gene inhibition. Moreover, we provide evidence that the protective effect of GM-CSF is related to its capacity to interfere with both ceramide generation and ceramide signaling. Negative regulation of the hTERT gene may represent one mechanism by which TNF interferes with normal hemopoiesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. G. Wooten-Blanks, P. Song, C. E. Senkal, and B. Ogretmen Mechanisms of ceramide-mediated repression of the human telomerase reverse transcriptase promoter via deacetylation of Sp3 by histone deacetylase 1 FASEB J, October 1, 2007; 21(12): 3386 - 3397. [Abstract] [Full Text] [PDF] A. K. Damjanovic, Y. Yang, R. Glaser, J. K. Kiecolt-Glaser, H. Nguyen, B. Laskowski, Y. Zou, D. Q. Beversdorf, and N.-p. Weng Accelerated Telomere Erosion Is Associated with a Declining Immune Function of Caregivers of Alzheimer's Disease Patients J. Immunol., September 15, 2007; 179(6): 4249 - 4254. [Abstract] [Full Text] [PDF]

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