Tsirpanlis George, Chatzipanagiotou Stylianos, Boufidou Fotini, Kordinas Vasileios, Zoga Margarita, Alevyzaki Fotini, Stamatelou Kyriaki, Frangou Eleni, Savva Lefkothea, Nicolaou Chrysoula
Department of Nephrology, General Hospital of Athens, Greece.
Nephrology (Carlton). 2006 Dec;11(6):506-9. doi: 10.1111/j.1440-1797.2006.00697.x.
Telomerase preserves telomeres' function and structure preventing cellular senescence. Its activity is reduced in peripheral blood mononuclear cells (PBMC) of haemodialysis (HD) patients. The purpose of this study is to investigate the potential correlation between increased oxidative stress/inflammation and telomerase activity in PBMC of HD patients.
Telomerase activity was measured by PCR-ELISA in PBMC isolated from a group of 42 HD patients and 39 subjects with estimated glomerular filtration rate >or=80 mL/min (control group). Serum oxidized low-density lipoprotein (ox-LDL), tumour necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) were also measured in both groups by ELISA.
Ox-LDL was negatively correlated to percentage telomerase activity in PBMC (r = -0.506, P = 0.000 in the whole group of 81 HD and normal subjects and r = -0.559, P < 0.001 in HD patients). TNF was also inversely associated with percentage telomerase activity in the whole group studied (r = -0.492, P = 0.000) while IL-10 was not. In stepwise multiple linear regression, taking into consideration the most important characteristics of the HD patients and control group, the only significant predictors for percentage telomerase activity in PBMC were ox-LDL and TNF (beta = -0.421, t = -4.083, P = 0.000 and beta = -0.381, t = -3.691, P = 0.000, respectively) while examining separately HD patients, the predictors for the same parameter were ox-LDL and HD duration (beta = -0.671, t = -4.709, P = 0.000 and beta = -0.349, t = -2.447, P = 0.023, respectively).
Ox-LDL serum level is inversely correlated to telomerase activity in PBMC of HD patients. Our study proposes a new consequence of increased oxidative stress in HD patients: the premature cellular senescence potentially related to atherosclerosis through LDL oxidation.
端粒酶可维持端粒的功能和结构,防止细胞衰老。血液透析(HD)患者外周血单个核细胞(PBMC)中端粒酶活性降低。本研究旨在探讨HD患者PBMC中氧化应激/炎症增加与端粒酶活性之间的潜在相关性。
采用PCR-ELISA法检测42例HD患者和39例估计肾小球滤过率≥80 mL/min的受试者(对照组)外周血单个核细胞中的端粒酶活性。两组均采用ELISA法检测血清氧化型低密度脂蛋白(ox-LDL)、肿瘤坏死因子-α(TNF-α)和白细胞介素-10(IL-10)。
ox-LDL与PBMC中端粒酶活性百分比呈负相关(81例HD患者和正常受试者的总体r = -0.506,P = 0.000;HD患者中r = -0.559,P < 0.001)。在整个研究组中,TNF也与端粒酶活性百分比呈负相关(r = -0.492,P = 0.000),而IL-10则无此相关性。在逐步多元线性回归中,考虑到HD患者和对照组的最重要特征,PBMC中端粒酶活性百分比的唯一显著预测因素是ox-LDL和TNF(β = -0.421,t = -4.083,P = 0.000;β = -0.381,t = -3.691,P = 0.000);单独分析HD患者时,同一参数的预测因素是ox-LDL和HD病程(β = -0.671,t = -4.709,P = 0.000;β = -0.349,t = -2.447,P = 0.023)。
HD患者血清ox-LDL水平与PBMC中端粒酶活性呈负相关。我们的研究提出了HD患者氧化应激增加的一个新后果:通过LDL氧化可能与动脉粥样硬化相关的细胞过早衰老。