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J Physiol Volume 556, Number 2, 369-385, April 15, 2004 DOI: 10.1113/jphysiol.2003.058420
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Induction, modification and accumulation of HSP70s in the rat liver after acute exercise: early and late responses

Beatriz González and Rafael Manso

Department of Molecular Biology, Centre of Molecular Biology ‘Severo Ochoa’ (CSIC-UAM), Autonomous University of Madrid, 28049-Cantoblanco, Spain

Liver cells synthesize HSP72, the cytosolic highly stress-inducible member of the 70 kDa family of heat-shock proteins (HSP70s), in response to acute exercise. This study was aimed at obtaining further insight into the physiological relevance of the hepatic stress response to exercise by investigating the induction and long-term maintenance of increased levels of HSP70s of the HSP and glucose-regulated protein (GRP) families, their post-translational modifications during or after exercise and the possible relation of HSP induction to oxidative stress. In a running rat model, acute exercise activated the synthesis and accumulation of HSP72, GRP75 and GRP78 in liver cells, pointing towards a multifactorial origin of this response. A peak HSP72 accumulation was observed shortly after exercise as a result of transcriptional activation. HSP72 was reduced shortly after exercise preceding the disappearance of its mRNA. Two further waves of HSP72 accumulation peaked 8 and 48 h after exercise without transcriptional activation. A transient increase in the proportion of acidic variants of HSP72 and HSP73 was also observed shortly after exercise as a result, at least in part, of protein phosphorylation. Free and protein-bound lipid peroxidation derivatives (TBARS) showed a tendency to increase in the early post-exercise and the free-to-protein-bound TBARS ratio decreased significantly after 2 h. During the early post-exercise period, protein-bound TBARS correlated positively with HSP72 and 73, but not with GRP75 or GRP78. Altogether, the reported results indicate that the early induction and post-translational modification of HSP70s in liver cells following exercise is a preliminary step of a series of long-lasting HSP70-related events, possibly designed to preserve liver cell homeostasis and to help provide a concerted response of the whole organism to physical stress.

(Received 26 November 2003; accepted after revision 28 January 2004; first published online 30 January 2004)
Corresponding author R. Manso: Centro de Biología Molecular ‘Severo Ochoa’ (CSIC-UAM), Universidad Autónoma de Madrid, E-28049 Cantoblanco, Madrid, Spain.  Email: rmanso{at}cbm.uam.es


Dedicated to Professor F. Mayor on the occasion of his 70th anniversary.




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