Functional properties of skeletal muscle from transgenic animals with upregulated heat shock protein 70

The influence of inducible heat stress proteins on protecting contracting s keletal muscle against fatigue-induced injury was investigated. A line of t ransgenic mice overexpressing the inducible form of the 72-kDa heat shock p rotein (HSP72) in skeletal muscles was used. We examined the relationship b etween muscle contractility and levels of the constitutive (HSC73) and indu cible (HSP72) forms of the 72-kDa heat shock protein in intact, mouse exten sor digitorum longus (EDL), soleus (SOL), and the diaphragm (DPH). In all t ransgenic muscles, HSP72 was expressed at higher levels compared with trans gene-negative controls, where HSP72 was below the level of detection. At th e same time, HSC73 levels were downregulated in all transgenic muscle types . Shipment-related stress caused an elevation in the levels of HSP72 in all muscles for 1 wk after arrival of the animals. We also found that, althoug h no statistical differences in response to intermittent fatiguing stimulat ion in the contractile properties of intact transgene-positive muscles comp ared with their transgene-negative counterparts were observed, the response of intact transgene-positive EDL muscles to caffeine was enhanced. These f indings demonstrate that elevated HSP72 does not protect EDL, SOL, or DPH m uscles from the effects of intermittent fatiguing stimulation. However, HSP 72 may influence the excitation-contraction coupling (ECC) process, either directly or indirectly, in EDL muscle. If the effects on ECC were indirect, then these results would suggest that manipulation of a specific gene migh t cause functional effects that seem independent of the manipulated gene/pr otein.