Marco
Grrrrrrr!
- Messages
- 2,386
- Location
- Near Cognac, France
Have we been missing a trick lately?
While there are numerous (often conflicting) studies on various immune parameters, cytokines, chemokines etc, one consistent finding is that ME/CFS is characterised by high levels of oxidative stress.
One aspect of oxidative stress and the body's response to it that hasn't had much attention is the influence of heat shocks proteins (HSPs). Perhaps they are a little too old school, but they are also a fundamental part of the body's response to 'stressors' of all types (heat, cold, exercise, infection, chemical, psychological stress etc). In fact, heat shock proteins should protect against any physiological stressor associated with day to day living and any dysfunction in the expression of HSPs would leave the body very exposed to ongoing oxidative stress leading to cell death and senescence (a reduction in HSP expression is associated with ageing).
I'm not going to wax lyrical here. Just provide a few comments and links for anyone interested.
On Heat shock Proteins generally
http://en.wikipedia.org/wiki/Heat_shock_protein
What should happen is that HSP expression remains at base levels until a potentially damaging stressor causes the rapid, massive and sustained release in order to prevent cellular damage from oxidative stress.
HSPs in ME/CFS
Three studies have found certain abnormalities in HSP production in ME/CFS patients compared to controls. HSP27 is chronically significantly raised in ME/CFS but, in response to exercise, production of HSPs (HSP27, 60 and 70) declines rapidly rather than remain elevated exposing cells to oxidative stress.
Thambirajah et al, 2008 (full paper) :
http://www.name-us.org/ResearchPage...idativeArticles/2008ChowHeatShockProteins.pdf
Jammes et al, 2009 (full paper) :
http://www.co-cure.org/Jammes.pdf
Jammes et al, 2011 (abstract only)
http://www.ncbi.nlm.nih.gov/pubmed/22112145
Interestingly, in this paper, they find this dysfunction most strongly associated with those reporting a prior viral illness of high intensity exercise.
Here's the description of the function of the relevant HSPs from Thambirajah et al :
In a nice piece of symmetry, normally HSP production peaks at 48 hours after exercise, at the time that markers of PEM appear to be most pronounced.
http://jap.physiology.org/content/101/1/176.full.pdf
The consequences of ongoing inadequate protection against oxidative stress are easy to imagine and this lack of protection negates the need to look for pathogens that cross the blood brain barrier. The absence of the protective effects of HSPs against oxidative stress can explain neurodegeneration.
Far from being a 'complex' or 'mysterious' disease, a deficient HSP response to stressors suggests a very fundamental systemic pathology with many downstream effects.
While there are numerous (often conflicting) studies on various immune parameters, cytokines, chemokines etc, one consistent finding is that ME/CFS is characterised by high levels of oxidative stress.
One aspect of oxidative stress and the body's response to it that hasn't had much attention is the influence of heat shocks proteins (HSPs). Perhaps they are a little too old school, but they are also a fundamental part of the body's response to 'stressors' of all types (heat, cold, exercise, infection, chemical, psychological stress etc). In fact, heat shock proteins should protect against any physiological stressor associated with day to day living and any dysfunction in the expression of HSPs would leave the body very exposed to ongoing oxidative stress leading to cell death and senescence (a reduction in HSP expression is associated with ageing).
I'm not going to wax lyrical here. Just provide a few comments and links for anyone interested.
On Heat shock Proteins generally
http://en.wikipedia.org/wiki/Heat_shock_protein
Upregulation in stress
Production of high levels of heat shock proteins can also be triggered by exposure to different kinds of environmental stress conditions, such as infection, inflammation, exercise, exposure of the cell to toxins (ethanol, arsenic, trace metals, and ultraviolet light, among many others), starvation, hypoxia (oxygen deprivation), nitrogen deficiency (in plants), or water deprivation. As a consequence, the heat shock proteins are also referred to as stress proteins and their upregulation is sometimes described more generally as part of the stress response.[8]
What should happen is that HSP expression remains at base levels until a potentially damaging stressor causes the rapid, massive and sustained release in order to prevent cellular damage from oxidative stress.
HSPs in ME/CFS
Three studies have found certain abnormalities in HSP production in ME/CFS patients compared to controls. HSP27 is chronically significantly raised in ME/CFS but, in response to exercise, production of HSPs (HSP27, 60 and 70) declines rapidly rather than remain elevated exposing cells to oxidative stress.
Thambirajah et al, 2008 (full paper) :
http://www.name-us.org/ResearchPage...idativeArticles/2008ChowHeatShockProteins.pdf
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.
Jammes et al, 2009 (full paper) :
http://www.co-cure.org/Jammes.pdf
Conclusions. The response of CFS patients to incremental exercise associates a lengthened and accentuated oxidative stress, which might result from delayed and insufficient Hsp production.
Jammes et al, 2011 (abstract only)
http://www.ncbi.nlm.nih.gov/pubmed/22112145
Interestingly, in this paper, they find this dysfunction most strongly associated with those reporting a prior viral illness of high intensity exercise.
The presence of stress factors in the history of CFS patients is associated with severe oxidative stress and the suppression of protective HSP27 and HSP70 responses to exercise
Here's the description of the function of the relevant HSPs from Thambirajah et al :
Small HSPs, such as HSP27, are important in microfilament organization, cell growth and differentiation, and in protecting cells against apoptosis induced by hyperthermia, inflammatory cytokines and oxidative stress.
HSP60 and HSP70 are involved in the oligomeric assembly and transport of peptides associated with the mitochondrial matrix.6 In addition to heat shock responses, HSP70 also mediates cyto-protection to oxidative stress.10 HSP90 is one of the most abundant chaperones in the eukaryotic cytosol, and plays a critical role in regulating cellular processes such as hormone signalling and cell cycle control.
In a nice piece of symmetry, normally HSP production peaks at 48 hours after exercise, at the time that markers of PEM appear to be most pronounced.
Exercise induced a significant (P 0.05) but variable increase in HSP70, heat shock cognate (HSC) 70, and HSP60 expression with peak increases (typically occurring at 48 h postexercise) to 210, 170, and 139% of preexercise levels, respectively.
http://jap.physiology.org/content/101/1/176.full.pdf
The consequences of ongoing inadequate protection against oxidative stress are easy to imagine and this lack of protection negates the need to look for pathogens that cross the blood brain barrier. The absence of the protective effects of HSPs against oxidative stress can explain neurodegeneration.
Far from being a 'complex' or 'mysterious' disease, a deficient HSP response to stressors suggests a very fundamental systemic pathology with many downstream effects.