Tsirpanlis George, Chatzipanagiotou Stylianos, Boufidou Fotini, Kordinas Vasileios, Alevyzaki Fotini, Zoga Margarita, Kyritsis Ilias, Stamatelou Kyriaki, Triantafyllis George, Nicolaou Chrysoula
Department of Nephrology, General Hospital of Athens, Athens, Greece.
Am J Nephrol. 2006;26(1):91-6. doi: 10.1159/000092031. Epub 2006 Mar 14.
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.
In PBMCs isolated from 42 HD and 39 non-renal-failure subjects of the same age (51.0 +/- 12.4 and 51.4 +/- 12.1 years, respectively) telomerase activity was measured using PCR-ELISA; the method was based on the telomeric repeat amplification protocol.
Telomerase activity in PBMCs was detected in 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-renal- failure (117 +/- 112 %) than in HD (47.6 +/- 57.1 %) subjects (p = 0.008). Detectable telomerase activity was lower in long-term than in short-term HD patients (13.3 +/- 8.9 vs. 75.0 +/- 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.
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.
端粒酶可维持端粒长度和结构,防止细胞衰老,而细胞衰老与染色体末端改变有关。我们推测血液透析(HD)患者外周血单个核细胞(PBMC)中端粒酶活性发生改变。为了研究这一推测以及端粒酶与炎症之间的关系,我们测定了终末期肾衰竭(ESRF)人群和非肾衰竭受试者组的PBMC及血清中这种逆转录酶的活性以及几种炎症标志物的水平。
从42例HD患者和39例年龄相同(分别为51.0±12.4岁和51.4±12.1岁)的非肾衰竭受试者中分离出PBMC,采用PCR-ELISA法测定端粒酶活性;该方法基于端粒重复序列扩增协议。
在18例(42.9%)HD患者和28例(71.8%)非肾衰竭受试者的PBMC中检测到端粒酶活性(p = 0.013)。在阳性受试者中,非肾衰竭受试者PBMC中的端粒酶活性百分比(117±112%)显著高于HD患者(47.6±57.1%)(p = 0.008)。长期HD患者中可检测到的端粒酶活性低于短期HD患者(分别为13.3±8.9%和75.0±64.8%,p = 0.015)。尽管HD组炎症指标(C反应蛋白、白细胞介素-6、IL-6、可溶性IL-6和可溶性gp130)较高,但与PBMC中的端粒酶活性无关。
HD患者PBMC中的端粒酶活性降低。似乎至少在该人群的这类细胞中,通过端粒酶活性评估的抗衰老能力发生了改变,且与尿毒症/HD治疗的慢性化有关。