SUMMARYWe hypothesised that activation of muscle afferents by fatigue triggers a widespread activation of heat shock proteins (HSPs) in resting muscles and different organs. In anaesthetised rats, HSP25 and HSP70 levels were determined in both tibialis anterior (TA) and extensor digitorum longus (EDL) muscles and in the diaphragm, kidney and brain by ELISA, which mostly identifies phosphorylated HSP, and western blotting. One TA muscle was electrically stimulated and tissues were sampled 10 or 60min after the stimulation had ended. The nerve supply to the stimulated TA or its counterpart in the contralateral limb was left intact or suppressed. In control rats, no muscle stimulation was performed and tissues were sampled at the same time points (10 or 60min). After TA stimulation, ELISA showed an increased HSP25 content in the contralateral TA, EDL and diaphragm at 10min but not at 60min, and HSP70 increased in all sampled tissues at 60min. Western blotting did not show any changes in HSP25 and HSP70 at 10min, while at 60min HSP25 increased in all sampled tissues except the brain and HSP70 was elevated in all tissues. Denervation of the contralateral non-stimulated limb suppressed HSP changes in TA and after denervation of the stimulated TA the widespread activation of HSPs in other organs was absent. Our data suggest that fatigue-induced activation of skeletal muscle afferents triggers an early increase in phosphorylated HSP25 in muscles and a delayed elevation of non-phosphorylated HSP25 and HSP70 in skeletal and respiratory muscles, kidney and brain.
Summary We already showed a widespread heat shock protein (HSP) response to fatigue of a single hindlimb muscle, responsible for a global adaptive response to an acute localized stress. We also demonstrated that the HSP response resulted from the activation of nerve afferents from the stimulated muscle. However, we did not examine the role played by the different muscle afferents as well as the efferent arm of HSP response. We here measured the changes in phosphorylated HSP25 (pHSP25) levels in resting hindlimb muscles, the diaphragm, kidney, and brain in response to a fatiguing stimulation of one tibialis anterior (TA) muscle which was repeated in five series of experiments: 1) intact muscle innervation, 2) during the selective procaine block of conduction in group IV muscle afferents, 3) after muscle nerve transection to suppress all the sensory messages, under pharmacological blockade of the 4) alpha adrenergic or 5) glutamatergic neurotransmission. The data showed that: 1) the pHSP25 response in hindlimb muscles resulted from the stimulation of both the groups III and IV muscle afferents while the pHSP25 response in the diaphragm, kidney, and brain resulted from the sole activation of the group IV fibres, 2) the blockade of alpha adrenergic, but not that of glutamatergic neurotransmission, suppressed the pHSP25 response in all the explored tissues except the brain. The present study highlights the role played by the groups III and IV muscle afferents in the fatigue-induced pHSP25 response and shows that the sympathetic nerve supply to the muscles and kidney represents the efferent arm of the pHSP25 activation. However, the pHSP25 changes in the brain cannot be explained by the pathways investigated here.
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