Co-activation of Akt, Nrf2, and NF-κB signals under UPRER in torpid Myotis ricketti bats for survival

Abstract

Bats hibernate to survive stressful conditions. Examination of whole cell and mitochondrial proteomes of the liver of Myotis ricketti revealed that torpid bats had endoplasmic reticulum unfolded protein response (UPRER), global reduction in glycolysis, enhancement of lipolysis, and selective amino acid metabolism. Compared to active bats, torpid bats had higher amounts of phosphorylated serine/threonine kinase (p-Akt) and UPRER markers such as PKR-like endoplasmic reticulum kinase (PERK) and activating transcription factor 4 (ATF4). Torpid bats also had lower amounts of the complex of Kelch-like ECH-associated protein 1 (Keap1), nuclear factor erythroid 2-related factor 2 (Nrf2), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) (p65)/I-κBα. Cellular redistribution of 78 kDa glucose-regulated protein (GRP78) and reduced binding between PERK and GRP78 were also seen in torpid bats. Evidence of such was not observed in fasted, cold-treated, or normal mice. These data indicated that bats activate Akt, Nrf2, and NF-κB via the PERK-ATF4 regulatory axis against endoplasmic reticulum stresses during hibernation.

Endoplasmic Reticulum Stress in Diabetic Nephrology: Regulation, Pathological Role, and Therapeutic Potential

“…Additionally, phosphorylated PERK induces the transcription factors ATF4 and C/EBP homologous protein (CHOP), which regulate the expression of genes involved in maintaining homeostasis [ 9 ]. Activated PERK also increases the expression of the transcription factor NRF2, which triggers an antioxidant response [ 10 , 11 ].…”

Unexpected expression of heat-activated transient receptor potential (TRP) channels in winter torpid bats and cold-activated TRP channels in summer active bats

“…Twenty-four 9-week-old C57BL/6J mice were purchased from Shanghai SLAC Laboratory Animal Co., Ltd. (China) and were maintained under a 12 h light-dark cycle at 23 °C. After one week of acclimation, the mice were randomly divided into four groups ( n =6 per group) and exposed for 1 h/day to 4 °C, 25 °C, 37 °C, and 40 °C, respectively ( Huang et al, 2020 ). These temperatures were chosen as they are in the temperature range whereby mice can adjust their physiological status subsequent to thermosensation by their Thermo-TRPs ( Hankenson et al, 2018 ).…”

“…Protein concentration was measured using a Quick Start Bradford protein assay kit (Bio-Rad, USA). Western blotting was carried out as described previously ( Han et al, 2015 ; Huang et al, 2020 ). Brain protein extracts prepared from mice or rats were used as positive controls, and an equal loading of the sample amount was monitored by Ponceau staining (Supplementary Data 3).…”

Biomimetics provides lessons from nature for contemporary ways to improve human health

“…The extremely high metabolism in bats not only increases the risk of ROS generation and DNA damage, but also causes a fever of 38-41 °C that may in itself reduce the viral load (73). The high risk of DNA damage may be one reason why bats, over evolution, have developed increased expression of Nrf2 (102) that protects bats during hibernation (103) in an state of increased endoplasmic reticulum stresses (159). The extraordinary immunology system of camelids also needs mentioning.…”