Expression of stress proteins and mitochondrial chaperonins in chronically stimulated skeletal muscle

Abstract

Molecular chaperones and cytosolic stress proteins are actively involved in the stabilization, import and refolding of precursor proteins into mitochondria. The purpose of the present study was to evaluate the relationship between mitochondrial content under steady-state conditions, and during the induction of organelle biogenesis, with the expression of stress proteins and mitochondrial chaperonins. A comparison of steady-state levels of mitochondrial enzyme activity [cytochrome c oxidase (CYTOX)] with chaperonin levels [the heat-shock protein HSP60, the glucose-regulated protein GRP75 (mtHSP70)] in striated muscles possessing a wide range of oxidative capacities revealed a proportional expression between the two. This relationship was disrupted by chronic contractile activity brought about by 10 days of 10 Hz stimulation of the tibialis anterior (TA) muscle, which induced 2.4-fold increases in CYTOX activity, but 3.2- and 9.3-fold increases in HSP60 and GRP75 respectively. The inducible stress protein HSP70i was detected at low levels in control TA muscle, and was increased 9.6-fold by chronic contractile activity, to values comparable with those found in the unstressed soleus muscle. This increase occurred in the absence of changes in type I MHC levels, indicating independent regulation of these genes. Despite the increases in HSP60 and HSP70i proteins, contractile activity did not alter their respective mRNA levels, illustrating post-transcriptional mechanisms of gene regulation during contractile activity. In contrast, the mRNA levels encoding the co-chaperonin CPN10 were increased 3.3-fold by contractile activity. Thus, the expression of individual mitochondrial chaperonins is independently regulated and uncoordinated. The extent of the induction of these stress proteins and chaperonins by contractile activity exceeded that of membrane enzymes (e.g. CYTOX). It remains to be determined whether this marked induction of proteins comprising part of the protein import machinery is beneficial for the translocation of enzyme precursors into the mitochondria during conditions of accelerated biogenesis.

Heat shock protein expression is increased in cardiac and skeletal muscles of Fischer 344 rats after endurance training

“…Thus, it appears that HSPs may play a role in protection not only in cardiac, but also in skeletal muscle. In mammalian muscle cells, the 60 kDa family of HSPs is increased both after acute exhaustive exercise (Locke et al 1990;Salo et al 1991) and 10 days of chronic contractile activity (Ornatsky et al 1995). Our data indicate that basal HSP 60 levels were 44, 43 and 67% greater in the LV, RV and SOL, respectively, of trained versus untrained rats, but they were not changed in AT or LG.…”

“…The physiological stress of exercise (Locke et al 1990(Locke et al , 1995Salo et al 1991) and exercise-like activities (Ornatsky et al 1995;Neuffer et al 1996) acutely elevates HSP expression. Locke et al (1990) have demonstrated that rodent skeletal muscle HSPs are increased after one bout of exhaustive exercise.…”

Mitochondrial Biogenesis in Skeletal Muscle: Exercise and Aging

“…In turn, activity-induced changes have been observed in Tom20, Hsp60 and mtHSP70 protein and cpn10 mRNA levels, as well as cytosolic concentrations of Hsp70 and MSF (13)(14)(15). Coincident with these changes is acceleration in the rate of protein import into the matrix.…”

Colocalisation of CD9 and mortalin in CD9-induced mitotic catastrophe in human prostate cancer cells

“…Mortalin is ubiquitously expressed, and so far has been detected in all mammalian cells analysed. This protein has been implicated in stress response (Ornatsky et al, 1995), muscle activity (Ibi et al, 1996), mitochondrial biogenesis (Schneider and Hood, 2000), control of cell proliferation (Kaul et al, 2000b), intracellular trafficking (Mizukoshi et al, 2001), differentiation (Xu et al, 1999) and tumorigenesis (Takahashi et al, 1994;Kaul et al, 1998;Wadhwa et al, 2006). Expression level of mortalin is frequently increased in tumours (Kaul et al, 2002;Dundas et al, 2005), where it is believed to cause inactivation of tumour suppressor protein TP53 .…”