Thambirajah Anita A, Sleigh Kenna, Stiver H Grant, Chow Anthony W
Department of Biochemistry and Microbiology,University of Victoria, Victoria, Canada.
Clin Invest Med. 2008 Dec 1;31(6):E319-27. doi: 10.25011/cim.v31i6.4917.
Since physical exertion is known to exacerbate the symptoms of chronic fatigue syndrome (CFS) and metabolic changes and including oxidative stress can modulate heat shock protein (HSP) expression responses, we sought to determine whether HSP expression is altered in CFS patients before and after exercise. Heat shock proteins (HSPs) in peripheral blood mononuclear cells (PBMC) were examined from 6 chronic fatigue syndrome (CFS) patients and 7 controls before and after a standardized treadmill exercise. Basal hsp27 was significantly higher among CFS patients compared to controls, and decreased immediately post-exercise, remaining below basal levels even at 7 days. A similar pattern was observed for HSP60, which gradually decreased in CFS patients but increased in controls post-exercise. These findings suggest an abnormal adaptive response to oxidative stress in CFS, and raise the possibility that HSP profiling may provide a more objective biologic marker for this illness.
HSP27, HSP60, HSP70 and HSP90 expression from 6 CFS patients and 7 age- and sex-matched controls were examined by western blot analysis of peripheral blood mononuclear cells immediately before, after, and at 1 day and 7 days following a standardized treadmill exercise.
Basal HSP27 was higher among CFS patients than in controls (0.54 +/- 0.13 vs. 0.19 +/- 0.06, mean +/- SEM; P < 0.01). In addition, these levels in CFS patients decreased immediately post-exercise (0.25 +/- 0.09; P < 0.05) and remained below basal levels at day 1 post-exercises (0.18 +/- 0.05; P < 0.05). P < 0.05). This declining expression of HSP27 during the post-exercise period among CFS patients was confirmed by one-way ANOVA analysis with repeated measures (P < 0.05). In contrast, HSP27 levels remained relatively constant following exercise among control subjects. Similar patterns of declining HSP levels in CFS patients were also observed for HSP60 (0.94 +/- 0.40 vs. 1.32 +/- 0.46; P < 0.05), and for HSP90 (0.34 +/- 0.09 vs. 0.49 +/- 0.10; P < 0.05) at day 7 post-exercise compared with basal levels, respectively. In contrast, HSP60 levels in control subjects increased at day 1 (1.09 +/- 0.27) and day 7 (1.24 +/- 0.50) post-exercise compared to corresponding levels immediately post-exercise (0.55 +/- 0.06) (P < 0.05, respectively).
These preliminary findings suggest an abnormal or defective adaptive response to oxidative stress in CFS, and raise the possibility that HSP profiling may provide a more objective biologic marker for this illness.
由于已知体力活动会加剧慢性疲劳综合征（CFS）的症状，且代谢变化（包括氧化应激）可调节热休克蛋白（HSP）的表达反应，我们试图确定CFS患者在运动前后HSP的表达是否发生改变。在标准化跑步机运动前后，对6例慢性疲劳综合征（CFS）患者和7例对照者的外周血单核细胞（PBMC）中的热休克蛋白（HSPs）进行了检测。与对照组相比，CFS患者的基础hsp27显著更高，运动后立即下降，甚至在7天时仍低于基础水平。HSP60也观察到类似模式，CFS患者中其逐渐下降，而对照组运动后增加。这些发现提示CFS患者对氧化应激存在异常的适应性反应，并增加了HSP谱分析可能为该疾病提供更客观生物标志物的可能性。
通过对6例CFS患者和7例年龄及性别匹配的对照者在标准化跑步机运动前、运动后、运动后1天和7天的外周血单核细胞进行蛋白质免疫印迹分析，检测HSP27、HSP60、HSP70和HSP90的表达。
CFS患者的基础HSP27高于对照组（0.54±0.13对0.19±0.06，平均值±标准误；P<0.01）。此外，CFS患者的这些水平在运动后立即下降（0.25±0.09；P<0.05），运动后1天仍低于基础水平（0.18±0.05；P<0.05）。通过重复测量的单因素方差分析证实了CFS患者运动后期间HSP27的这种下降表达（P<0.05）。相比之下，对照组运动后HSP27水平保持相对稳定。在运动后7天，CFS患者中HSP60（0.94±0.40对1.32±0.46；P<0.05）和HSP90（0.34±0.09对0.49±0.10；P<0.05）与基础水平相比也观察到类似的下降模式。相比之下，对照组运动后1天（1.09±0.27）和7天（1.24±0.50）的HSP60水平与运动后立即的相应水平（0.55±0.06）相比有所增加（分别为P<0.05）。
这些初步发现提示CFS患者对氧化应激存在异常或有缺陷的适应性反应，并增加了HSP谱分析可能为该疾病提供更客观生物标志物的可能性。
