Original Report: Laboratory Investigation American
Journal of
Nephrology
Received: August 29, 2005 Accepted: December 12, 2005 Published online: March 14, 2006
Am J Nephrol 2006;26:91–96 DOI: 10.1159/000092031
Telomerase Activity Is Decreased in Peripheral Blood Mononuclear Cells of Hemodialysis Patients George Tsirpanlis a Stylianos Chatzipanagiotou b Fotini Boufidou b Vasileios Kordinas b Fotini Alevyzaki a Margarita Zoga b Ilias Kyritsis a Kyriaki Stamatelou c George Triantafyllis a Chrysoula Nicolaou b a
Department of Nephrology, General Hospital of Athens, b Department of Medical Biopathology, Eginition Hospital, Medical School, University of Athens, and c Renal Unit, Blue Cross Hospital, Athens, Greece
Key Words Telomeres Interleukin-6 Soluble interleukin-6 receptor Soluble gp130 C-reactive protein Peripheral blood mononuclear cells Serum albumin
Abstract Background: Telomerase preserves telomere length and structure, preventing cellular senescence, which is associated with alteration of the chromosomal ends. We hypothesized that telomerase activity is altered in peripheral blood mononuclear cells (PBMCs) of hemodialysis (HD) patients. To investigate this hypothesis as well as the relationship between telomerase and inflammation, we measured the activity of this reverse transcriptase as well as the level of several inflammatory markers in PBMCs and serum of an end-stage renal failure (ESRF) population and a non-renal-failure group of subjects. Methods: In PBMCs isolated from 42 HD and 39 non-renal-failure subjects of the same age (51.0 8 12.4 and 51.4 8 12.1 years, respectively) telomerase activity was measured using PCR-ELISA; the method was based on the telomeric repeat amplification protocol. Results: Telomerase activity in PBMCs was detected in
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18 (42.9%) HD and 28 (71.8%) non-renal-failure subjects (p = 0.013). Among positive subjects, percent telomerase activity in PBMCs was significantly higher in non-renalfailure (117 8 112 %) than in HD (47.6 8 57.1 %) subjects (p = 0.008). Detectable telomerase activity was lower in long-term than in short-term HD patients (13.3 8 8.9 vs. 75.0 8 64.8%, respectively, p = 0.015). Although higher in HD group, inflammatory indexes (C-reactive protein, interleukin-6, IL-6, soluble IL-6 and soluble gp130) were not correlated to telomerase activity in PBMCs. Conclusion: Telomerase activity in PBMCs is reduced in HD patients. It seems that, at least in this type of cell in this population, defense from senescence, as assessed by telomerase activity, is altered and associated with the chronicity of uremia/HD procedure. Copyright © 2006 S. Karger AG, Basel
Introduction
Cellular senescence is an important aspect of cell behavior and seems to occur either after an extended period of cell divisions (‘replicative senescence’) or more rapidly in response to various physiologic stresses (‘stress-in-
George Tsirpanlis, MD Amarysias Artemidos 34C Ag. Thomas, Marousi GR–15124 Athens (Greece) Tel./Fax +30 210 685 4393, E-Mail
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Table 1. Characteristics and serum inflammatory markers of the subjects included in the study
Non-renal-failure subjects (n = 39) Age, years 51.4812.1 Sex, F/M 23/16 BMI, kg/m2 25.183.9 Smoking 13 Diabetes 1 Hypertension 9 Atherosclerosisa 3 Angiotensin-converting enzyme inhibitors 3 Angiotensin receptor antagonists 3 Ca channels blockers 4 Aspirin, 100 mg/day 3 C-reactive protein, mg/l 2.582.3 Interleukin-6, IL-6, pg/ml 2.680.7 Soluble IL-6 receptor, sIL-6R, ng/ml 2518106 Soluble gp130, sgp130, ng/ml 365861 (IL-6 ! sIL-6R)/sgp130 1.981.2 Serum albumin, g/l 4.880.3
Hemodialysis p patients (n = 42) 51.0812.4 20/22 26.184.8 9 3 16 9 8 5 9 8 7.688.2 8.2810.1 3968111 406894 9.0811.9 4.480.3
