Activation Of Survival Signals In Bats Against Stresses During Hibernation

Hibernation is a unique ability of some animals to survive cold and food shortage.It consists of repeated cycles of torpor-arousal states.At torpor,some mammals reduce their body temperature,metabolic rate,cardiac rhythm and oxygen consumption.However,these physiological depressions recover very quickly upon arousal with no severe damage of organs.The molecular mechanisms underlying hibernation are not clear.In this study,we use shotgun proteomics,bioinformatics,and biochemistry analyses to explore the mechanism of tissue protection and metabolic regulation in Myotis pilosus during hibernation.Results of shotgun proteomics showed differential expression profiles of liver and liver mitochondrial proteins of Myotis pilosus bats at torpid(T),2 h-aroused,24 h-aroused,and summer-active(SA)states.Using the principal component analysis(PCA),we found that the significant difference of the profiles exists among T,24 h-aroused,and SA bats.The GO enrichment analysis showed that many proteins identified are involved in the process of translation,metabolism and survival adaption.Four major hubs were seen in the protein-protein interaction(PPI)map of identified proteins,and those with significant expression changes are mostly located in the hub regions.The IPA analysis showed that EIF2 and PI3K/Akt signalings,and unfolded protein response(UPR)is activated during bat torpor.Taken together,we hypothesize that bats launch a UPR/EIF2 signal during torpor.Activation of the UPR/EIF2 signaling in torpid bats was confirmed by WB and Co-IP,and the activation of Akt/Nrf2/NF-?B signalings was also found,suggesting the important role of these signals in the survival adaption of bat torpor.It is highly possible that UPR/EIF2 signaling and Akt/Nrf2/NF-?B signalings synergistically control the molecular mechanism in protection of torpid bats against cold winter.We also found that both glycometabolism and amino acid metabolism are downregulated in bats during hibernation,while the gluconeogenesis,glycogen metabolism,and the metabolism of glucgenic and ketogenic amino acids are upregulated.Moreover,different isoform of enzymes involved in lipid metabolism were up-regulated but some enzymes in the metabolism of unsaturated fatty acids may be down-regulated during hibernation.In summary,we performed a systematic study to reveal for the first time the critical role of UPR/EIF2 and Akt/Nrf2/ NF-?B signalings in bat hibernation,which may aid in organ preservation during transplantation.