scholarly journals Differential heat shock protein responses to strenuous standardized exercise in chronic fatigue syndrome patients and matched healthy controls

2008 ◽  
Vol 31 (6) ◽  
pp. 319 ◽  
Author(s):  
Anita A Thambirajah ◽  
Kenna Sleigh ◽  
H. Grant Stiver ◽  
Anthony W Chow
Keyword(s):  
Oxidative Stress ◽  
Heat Shock ◽  
Chronic Fatigue Syndrome ◽  
Mononuclear Cells ◽  
Chronic Fatigue ◽  
Peripheral Blood Mononuclear ◽  
Post Exercise ◽  
Fatigue Syndrome ◽  
Before And After ◽  
Biologic Marker

Purpose: 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. Methods: 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. Results: 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). Conclusion: 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.

scholarly journals A SWATH-MS analysis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome peripheral blood mononuclear cell proteomes reveals mitochondrial dysfunction

2020 ◽  
Author(s):  
Eiren Sweetman ◽  
Torsten Kleffmann ◽  
Christina Edgar ◽  
Michel de Lange ◽  
Rosamund Vallings ◽  
...  
Keyword(s):  
Chronic Fatigue Syndrome ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Chronic Fatigue ◽  
Myalgic Encephalomyelitis ◽  
Differentially Expressed ◽  
Control Group ◽  
Peripheral Blood Mononuclear ◽  
Fatigue Syndrome ◽  
Ms Analysis

Abstract Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a serious and complex physical illness that affects all body systems with a multiplicity of symptoms, but key hallmarks of the disease are pervasive fatigue and ‘post-exertional malaise’, exacerbation after physical and/or mental activity of the intrinsic fatigue and other symptoms that can be highly debilitating and last from days to months. Although the disease can vary widely between individuals, common symptoms also include pain, cognitive deficits, sleep dysfunction, as well as immune, neurological and autonomic symptoms. Typically, it is a very isolating illness socially, carrying a stigma because of the lack of understanding of the cause and pathophysiology.Methods: To gain insight into the pathophysiology of ME/CFS, we examined the proteomes of peripheral blood mononuclear cells (PBMCs) by SWATH-MS analysis in a small well-characterised group of patients and matched controls. A principal component analysis (PCA) was used to stratify groups based on protein abundance patterns, which clearly segregated the majority of the ME/CFS patients (9/11) from the controls. This majority subgroup of ME/CFS patients was then further compared to the control group. Results: A total of 60 proteins in the ME/CFS patients were differentially expressed (P < 0.01, Log10 (Fold Change) > 0.2 and < -0.2). Comparison of the PCA selected subgroup of ME/CFS patients (9/11) with controls increased the number of proteins differentially expressed to 99. Of particular relevance to the core symptoms of fatigue and post-exertional malaise experienced in ME/CFS, a proportion of the identified proteins in the ME/CFS groups were involved in mitochondrial function, oxidative phosphorylation, electron transport chain complexes, and redox regulation. A significant number were also involved in previously implicated disturbances in ME/CFS, such as the immune inflammatory response, DNA methylation, apoptosis and proteasome activation. Conclusions: The results from this study support a model of deficient ATP production in ME/CFS, compensated for by upregulation of immediate pathways upstream of Complex V that would suggest an elevation of oxidative stress. This study and others have found evidence of a distinct pathology in ME/CFS that holds promise for developing diagnostic biomarkers.

Sign in / Sign up

Export Citation Format

Share Document