Tissue‐specific response of the RB‐E2F1 complex during mammalian hibernation

Abstract

Metabolic rate depression during prolonged bouts of torpor is characteristic of mammalian hibernation, reducing energy expenditures over the winter. Cell cycle arrest is observed in quiescent cells during dormancy, partly due to the retinoblastoma (Rb) protein at G 1 /S, given cell division and proliferation are metabolic-costly processes. Rb binds to E2F transcription factors and recruits corepressors (e.g., SUV39H1) to E2F target genes, blocking their transcription and cell cycle passage. Phosphorylation by cyclin-CDK complexes at S780 or S795 abolishes Rb-mediated repression, allowing transition into S phase. The present study compares Rb-E2F1 responses between euthermic and torpid states in five organs (brain, heart, kidney, liver, skeletal muscle) of 13-lined ground squirrels (Ictidomys tridecemlineatus). Immunoblotting assessed the expression of Rb, pRb (S780, S795), E2F1, and SUV39H1. Our findings demonstrate multi-tissue upregulation of Rb and SUV39H1 during torpor, with tissue-specific changes to E2F1 and pRb (S780), suggesting Rb-E2F1 contributes to cell cycle control in hibernation.

Torpor‐responsive microRNAs in the heart of the Monito del monte, Dromiciops gliroides

“…[10][11][12] Additionally, hibernators utilize tissue preservation strategies including chaperone proteins and antioxidant defenses to prepare for oxidative stress during arousal, [13][14][15][16][17][18][19] as well as various transcription factors to regulate gene expression. [20][21][22][23][24][25] Understanding the molecular mechanisms mammalian hibernators utilize to survive the stresses associated with torpor and arousal could potentially be applied to human medicine, particularly in the development of therapeutics for ischemia/reperfusion injuries and improved organ transplantation. 2,11,26,27 There are many regulatory mechanisms that contribute to the entrance into and maintenance of hibernation by altering gene expression to suppress nonessential proteins, while allowing for the expression of key prosurvival pathways.…”

“…In contrast to homeotherms who suffer deleterious arrythmias during hypothermia, heterotherms can maintain cardiac function at low T b despite increased blood viscosity and peripheral resistance via reversible cardiac hypertrophy and improved contractility 10–12 . Additionally, hibernators utilize tissue preservation strategies including chaperone proteins and antioxidant defenses to prepare for oxidative stress during arousal, 13–19 as well as various transcription factors to regulate gene expression 20–25 . Understanding the molecular mechanisms mammalian hibernators utilize to survive the stresses associated with torpor and arousal could potentially be applied to human medicine, particularly in the development of therapeutics for ischemia/reperfusion injuries and improved organ transplantation 2,11,26,27 …”