Elevated expression of protein biosynthesis genes in liver and muscle of hibernating black bears (Ursus americanus)

Abstract

We conducted a large-scale gene expression screen using the 3,200 cDNA probe microarray developed specifically for Ursus americanus to detect expression differences in liver and skeletal muscle that occur during winter hibernation compared with animals sampled during summer. The expression of 12 genes, including RNA binding protein motif 3 (Rbm3), that are mostly involved in protein biosynthesis, was induced during hibernation in both liver and muscle. The Gene Ontology and Gene Set Enrichment analysis consistently showed a highly significant enrichment of the protein biosynthesis category by overexpressed genes in both liver and skeletal muscle during hibernation. Coordinated induction in transcriptional level of genes involved in protein biosynthesis is a distinctive feature of the transcriptome in hibernating black bears. This finding implies induction of translation and suggests an adaptive mechanism that contributes to a unique ability to reduce muscle atrophy over prolonged periods of immobility during hibernation. Comparing expression profiles in bears to small mammalian hibernators shows a general trend during hibernation of transcriptional changes that include induction of genes involved in lipid metabolism and carbohydrate synthesis as well as depression of genes involved in the urea cycle and detoxification function in liver. gene expression; hibernation; translation; RNA binding protein motif 3 MAMMALIAN HIBERNATION IS a physiological and behavioral adaptation involving a coordinated suppression of heat production and body temperature wherein whole body metabolism and energy demand are significantly reduced over several days to several months. During hibernation, heart and respiration rates, blood flow, and oxygen consumption decrease dramatically to Ͻ10% of normal or basal rates (2, 4). These physiological changes do not represent a loss of homeostasis but instead are precisely controlled and spontaneously reversible, and they allow individual animals to survive highly seasonal or unpredictable environments where food availability becomes lacking (7, 12). The molecular and genetic basis of hibernation in small mammals has only recently begun to be described, and little is known about its evolutionary history. Hibernating species have been found in diverse families among seven orders of mammals (26), however, and the interspersed phylogenetic distribution of hibernating and nonhibernating species has led to the hypothesis that rather than requiring the creation of novel gene products, hibernation results from the differential expression of genes that exist widely among mammals (35).Microarray technology provides powerful means for the unbiased detection of differences in expression of thousands of genes in a single hybridization experiment (14). In contrast to single-gene expression analysis, the genome-wide approach also allows for identification of coordinated transcriptional changes in functional groups of regulatory genes within metabolic and signaling pathways. Recent studies of differential gen...

Dynamic changes in global and gene specific DNA methylation during hibernation in adult thirteen-lined ground squirrels,Ictidomys tridecemlineatus

“…In the liver, mbd3 and mecp2 mRNA levels differed between animals that were euthermic in the cold room and those in early arousal. We speculate that mbd3 transcription may support the activation of rRNA, as seen in previous studies (Brown and Szyf, 2007), consistent with the need for rapid reactivation of liver ribosomal protein synthesis when animals arouse from bouts of torpor (Epperson et al, 2004;Fedorov et al, 2009). Additionally, in muscle, MeCp2 has been reported to be involved in myogenesis as its role in forming pericentric heterochromatic centers is important for differentiation (Brero et al, 2005).…”

Skeletal muscles of hibernating brown bears are unusually resistant to effects of denervation

“…Thus, protection of skeletal muscles from the usual deleterious effects of disuse is not intrinsic to bears year-round and arises from changes in bear physiology occurring during hibernation. Consistent with this finding, gene expression for protein catabolism is downregulated and for protein synthesis is upregulated in skeletal muscle, liver and heart tissues of hibernating black bears relative to summer-active bears (Fedorov et al, 2009;Fedorov et al, 2011).…”

Prevention of muscle wasting and osteoporosis: the value of examining novel animal models

“…Rates of both protein degradation and synthesis can be reduced by up to 70% in the skeletal muscle of hibernating bears (Lohuis et al, 2007). However, more recent studies found increased expression of mRNAs largely involved in protein biosynthesis and ribosome biogenesis in the muscles of both hibernating bears and arctic ground squirrels relative to those of summer active animals, suggesting that induction of translation could be enhanced at different stages of hibernation (Fedorov et al, 2014(Fedorov et al, , 2009. Despite the need for global suppression of energetically expensive processes such as transcription and translation during dormancy (Storey and Storey, 2010), a number of recent studies have emphasised the importance of maintaining protein synthesis in hibernating muscle through activation of the mTOR signalling cascade (Andres-Mateos et al, 2013;Fedorov et al, 2014;Lee et al, 2010;Nowell et al, 2011).…”