Up-regulation of a thioredoxin peroxidase-like protein, proliferation-associated gene, in hibernating bats

Two-dimensional gel electrophoresis was used to assess differential protein expression between euthermic and hibernating states in heart of Myotis lucifugus. A hibernation-induced protein was identified by mass spectrometry as a thioredoxin peroxidase-like protein known as PAG. Western blotting confirmed up-regulation (>2-fold) and RT-PCR also revealed up-regulation (>5-fold) of pag mRNA. Cloning revealed a highly conserved sequence suggesting a conserved function for PAG. Oxidative stress markers, p-IκB-α (Ser 32) and p-HSP27 (Ser 78/82), were also up-regulated in heart and skeletal muscle during hibernation. Although there are selected increases in gene/protein expression during hibernation, general translation inhibition occurs as part of metabolic rate depression. This was confirmed by elevated levels of the inactive forms of the eIF2α (Ser 51) in both heart and skeletal muscle (2- to 5-fold higher than in euthermia) and the eEF2 (Thr 51) in skeletal muscle (a 15-fold increase). This study suggests that hibernators may use up-regulation of specific proteins to counteract oxidative stress.