Activation of Akt, Nrf2, and NF-κB signal transduction pathways in the liver as a mechanism of survival for torpid Myotis ricketti Bats

ABSTRACT: Unfolded protein accumulation in the lumen of endoplasmic reticulum (ER) induced by cold exposure is termed UPRER. Some mammals hibernate to overcome cold winter. We investigated whether hibernating bats are under UPRER and activate Akt, Nrf2, and NF-κB signaling pathways that are critical for cell survival against cold. Results of Western blotting showed that several UPRER marker proteins such as PERK and ATF4 had a higher abundance in torpid than in active bats. Cellular redistribution of GRP78 and a lower degree of binding between PERK and GRP78 were also seen in torpid bats, suggesting the occurrence of UPRER. Results also showed that torpid bats had a higher amount of p-Akt (Ser473), a higher ratio of p-Akt (Ser473)/Akt, a lower amount of Keap1/Nrf2 and NF-κB (p65)/I-κBα complexes, and a higher degree of NF-κB (p65) nuclear translocation than active bats, indicating simultaneous activation of Akt, Nrf2, and NF-κB during hibernation. Evidence of such activation was not observed in fasted, cold-treated, or normal mice. Using PPI network and IPA analyses, we examined the proteomes of liver and liver mitochondria of bats and found a global metabolic adjustment and survival adaptation in response to UPRER in hibernating bats. Our data provide the first molecular evidence of a complex cross talk involving Akt, Nrf2, and NF-κB via the PERK-EIF2-ATF4 regulatory axis under UPRER in bats to ensure their survival during hibernation.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Myotis Ricketti

TISSUE(S): Liver

SUBMITTER: Chen-Chung Liao  

LAB HEAD: Chen-Chung Liao

PROVIDER: PXD016109 | Pride | 2020-11-17

REPOSITORIES: Pride