HSP70 expression: does it a novel fatigue signalling factor from immune system to the brain?

Abstract

Integrative physiology studies have shown that immune system and central nervous system interplay very closely towards behavioural modulation. Since the 70-kDa heat shock proteins (HSP70s), whose heavy expression during exercise is well documented in the skeletal muscle and other tissues, is also extremely well conserved in nature during all evolutionary periods of species, it is conceivable that HSP70s might participate of physiologic responses such as fatigue induced by some types of physical exercise. In this way, increased circulating levels of extracellular HSP70 (eHSP70) could be envisaged as an immunomodulatory mechanism induced by exercise, besides other chemical messengers (e.g. cytokines) released during an exercise effort, that are able to binding a number of receptors in neural cells. Studies from this laboratory led us to believe that increased levels of eHSP70 in the plasma during exercise and the huge release of eHSP70 from lymphocytes during high-load exercise bouts may participate in the fatigue sensation, also acting as a danger signal from the immune system.

Mechanisms of PEDF-mediated protection against reactive oxygen species damage in diabetic retinopathy and neuropathy

“…Several inflammatory stimuli, such as TNFa, and also elevated levels oxidative stress can promote specific signal transducing pathways to enable phosphorylation of the IkB and subsequent degradation by the 26S proteosome (Sethi et al 2008). The phosphorylation of IkB releases NFkB from IkB protein and permits NFkB to translocate to the nucleus (Heck et al 2011). The subunit composition of NFkB can vary, although NFkB p65 (Rel A) and NFkB p50 (NFkB1) are the classical NFkB pathway components studied in inflammation (Sethi et al 2008).…”

Salivary extracellular heat shock protein 70 (eHSP70) levels increase after 59 min of intense exercise and correlate with resting salivary secretory immunoglobulin A (SIgA) levels at rest

“…Training adaptation includes exercise tolerance. It is possible that exercise-induced eHSP70 might increase inflammation, thereby inducing fatigue sensation (Heck et al 2011). Therefore, the change of salivary eHSP70 might describe the inflammatory status and relative fatigue sensation.…”

A Novel L-Arginine/L-Glutamine Coupling Hypothesis: Implications for Type 1 Diabetes

“…As recently reviewed (Heck et al, 2011), physical exercise and its inherent physiological alterations induce HSP70 expression in many tissues and cell types, not only in the muscle cells. The breakdown of cell homeostasis produced by modifications in temperature, pH, ion concentrations, oxygen partial pressure, glycogen/glucose availability, and ATP depletion are among the factors that activate HSP70 synthesis during exercise (Noble et al, 2008).…”

“…Traditionally, research groups indistinctly use HSP70 as a unified term for both inducible (72 kDa, HSP72 encoded by the HSPA1A human gene) and constitutive (73 kDa, HSP73 or HSC70, for heat shock cognate protein, encoded by the human HSPA8 gene whose product differs from HSPA1A protein by only 2 amino acids, Kampinga et al, 2009;Tavaria et al, 1996;Arya et al, 2007;Tavaria et al, 1995). However, HSP70 is the preferable form to be used only when one refers to the inducible HSP72 protein encoded by HSPA1A gene (Heck et al, 2011). Many different events can induce HSP expression, among them are environmental, pathological and physiological factors, such as heavy metal exposure, UV radiation, amino acid analogues, bacterial or viral infection, inflammation, cyclo-oxygenase inhibitors (including acetylsalicylic acid), oxidative stress, cytostatic drugs, growth factors, cell differentiation and tissue development, which strongly activate the main eukaryotic heat shock transcription factor, HSF-1, leading to HSP70 expression (Lindquist & Craig, 1988).…”