Exercise-induced muscle damage and inflammation: re-evaluation by proteomics

Using proteomics combined with immunohistochemistry (IHC), we re-evaluated our previous hypothesis that voluntary eccentric exercise does not result in inflammation or necrosis while it does lead to muscular adaptation/remodeling through Z-band related proteins. Muscle biopsies from m. vastus lateralis were taken from five control and five exercised subjects 48 h after 45 min of downhill running. General muscle morphology was examined using histology and histochemistry. Proteomics was used to reveal protein profiles and novel proteins. IHC with specific antibody against three Z-band related proteins identified by proteomics was also performed. General morphology showed no muscle degeneration or inflammation in any exercised biopsy. Proteomics revealed that out of 612 individual protein spots, the exercised biopsy presented three proteins with significant (p < 0.05) higher expression ratio and four proteins of lower ratio compared to controls. Four of the proteins desmin, actin, Rab-35 and LDB3 are Z-band related; the former two have long been the focus of interest and were found to be up-regulated in the study; the latter two are Z-band assembly/stabilization protein and were for the first time observed to be down-regulated in exercised muscles. The other three proteins are related with either cellular metabolism or calcium homeostasis and none is related with muscle necrosis or inflammation. IHC observations that both desmin and actin were increased whereas LDB3 was completely absent in some focal areas are consistent with proteomic results and with our previous observations. The results of the study confirmed our previous findings and therefore strengthened the hypothesis that voluntary eccentric exercise does not cause human muscle necrosis or inflammation; instead, muscular remodeling occurs specifically through Z-band related proteins.