Transgenic overexpression of heat shock protein 72 in mouse muscle protects against exhaustive exercise-induced skeletal muscle damage

Abstract

Lifelong overexpression of heat shock protein (HSP) 72 in skeletal muscle is known to protect against age-related oxidative stress and muscle damage. This study aimed to ascertain whether exhaustive exercise (EE)-induced muscle fatigue and damage can be prevented by lifelong overexpression of HSP72 in skeletal muscle. Transgenic mice heterozygous for the porcine HSP70.2 gene ([+]HSP72) and transgene-negative littermate controls ([-]HSP72) were subjected to an EE protocol. Mice were randomly divided into four groups: sedentary [-]HSP72, sedentary [+]HSP72, EE [-]HSP72, and EE [+]HSP72. Animals were killed 82 minutes after the start of EE to determine muscular levels of HSP72, serum levels of superoxide dismutase (SOD, an antioxidant enzyme) and lactate (an indicator of muscle fatigue), muscular levels of matrix metalloproteinase (an indicator of inflammatory myopathies), and muscular damage. During the test, the latency value for the occurrence of EE was 79-85 minutes and 100-110 minutes for [-]HSP72 and [+]HSP72 mice, respectively. After EE, [+]HSP72 mice had significantly higher serum SOD and significantly lower serum lactate, muscular matrix metalloproteinase or myeloperoxidase activity, and muscle damage compared to [-]HSP72 mice. The results suggest that HSP72 overexpression in skeletal muscle may improve muscle fatigue and damage in EE by reducing oxidative damage and phagocytic infiltration, at least in mice.