Dataset Information

Proteogenomic analysis in hibernating mammal suggests contribution of skeletal muscle physiology to hibernation phenotype

ABSTRACT: Mammalian hibernation is a strategy employed by many species to survive fluctuations in resource availability and environmental conditions. Hibernating mammals endure conditions of dramatically depressed heart rate, body temperature, and oxygen consumption; yet show no typical pathological response. Because of the high abundance and metabolic cost of skeletal muscle, not only must it adjust to the constraints of hibernation, but is positioned to play a more active role in the initiation and maintenance of the hibernation phenotype. In this study, MS/MS proteomic data were searched against a custom database of transcriptomic and genomic protein predictions built using the platform GalaxyP. This proteogenomic approach allows for a thorough investigation of skeletal muscle protein expression throughout the circannual cycle of the 13-lined ground squirrel. Of the 1,563 proteins identified by these methods, 232 were differentially expressed. Not only do these data support previously reported physiological transitions, they also offer insight into specific mechanisms of how their muscles might be reducing nitrogenous waste, preserving mass and function, and signaling to other tissues. Additionally, the combination of proteomic and transcriptomic data provides unique opportunities for determining the level of post-transcriptional regulation throughout the year and improving the genomic annotation of this non-model organism.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Spermophilus Tridecemlineatus (thirteen-lined Ground Squirrel)

TISSUE(S): Skeletal Muscle

SUBMITTER: Kyle Anderson

LAB HEAD: Matthew T. Andrews

PROVIDER: PXD003188 | Pride | 2018-07-11

REPOSITORIES: Pride

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Publications

Characterizing Cardiac Molecular Mechanisms of Mammalian Hibernation via Quantitative Proteogenomics.

Vermillion Katie L KL Jagtap Pratik P Johnson James E JE Griffin Timothy J TJ Andrews Matthew T MT

Journal of proteome research 20151023 11

This study uses advanced proteogenomic approaches in a nonmodel organism to elucidate cardioprotective mechanisms used during mammalian hibernation. Mammalian hibernation is characterized by drastic reductions in body temperature, heart rate, metabolism, and oxygen consumption. These changes pose significant challenges to the physiology of hibernators, especially for the heart, which maintains function throughout the extreme conditions, resembling ischemia and reperfusion. To identify novel card ...[more]

PMID: 26435507

Publication: 1/2

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Project description:During the winter, hibernating mammals undergo extreme changes in physiology which allow them to survive without access to food. These animals enter a state of torpor, which is characterized by a decreased metabolism, near-freezing body temperatures, and a dramatically reduced heart rate. The neurochemical basis of this regulation is largely unknown. Based on prior evidence suggesting that the peptide-rich hypothalamus plays critical roles in hibernation, we hypothesized that changes in specific cell-cell signaling peptides (neuropeptides and peptide hormones) underlie physiological changes during torpor/arousal cycles. To test this hypothesis, we used a mass spectrometry-based peptidomics approach to examine seasonal changes of endogenous peptides that occur in the hypothalamus and pituitary of a model hibernating mammal, the thirteen-lined ground squirrel (Ictidomys tridecemlineatus). In the pituitary, we observed changes in a number of distinct peptide hormones as animals prepare for torpor in October, exit torpor in March, and progress from Spring (March) to Fall (August). In the hypothalamus, we observed an overall increase in neuropeptides in October (pre-torpor), a decrease as the animal enters torpor, and an increase in a subset of neuropeptides during normothermic interbout arousals. Notable changes were observed for feeding regulatory peptides from NPY and proSAAS prohormones, opioid peptides from PENK, PDYN, and POMC prohormones, and a number of peptides without well-established functions. In contrast to transcriptome and antibody-based measurements, our mass spectrometry-based approach allowed the identification and measurement of the final processed forms of these peptides after extensive post-translational modifications. Overall, our study provides critical insight into changes in endogenous peptides in the hypothalamus and pituitary during mammalian hibernation that were not available from transcriptome measurements. Understanding the molecular basis underlying the hibernation phenotype may pave the way for future efforts to employ hibernation-like strategies for organ preservation, combating obesity, and treatments for stroke.

Project description:Hibernation is energy saving adaptation involving suppression of activity to survive in highly seasonal environments. Immobility and disuse generate muscle loss in most mammalian species. In contrast to other mammals, bears and ground squirrels demonstrate limited muscle atrophy over the physical inactivity of winter hibernation. This suggests that hibernating mammals have adaptive mechanisms to prevent disuse muscle atrophy. To identify common transcriptional program underlying molecular mechanisms preventing muscle loss, we conducted a large-scale gene expression screening in hind limb muscles comparing hibernating and summer active black bears and arctic ground squirrels by the use of custom 9,600 probe cDNA microarrays. The molecular pathway analysis showed an elevated proportion of overexpressed genes involved in all stages of protein biosynthesis and ribosome biogenesis in muscle of both species during hibernation that implies induction of translation at different hibernation states. The induction of protein biosynthesis likely contributes to attenuation of disuse muscle atrophy through prolonged periods of immobility and starvation. This adaptive mechanism allows hibernating mammals to maintain full musculoskeletal function and preserve mobility during and immediately after hibernation, thus promoting survival. The lack of directional changes in genes of protein catabolic pathways does not support the importance of metabolic suppression for preserving muscle mass during winter. Coordinated reduction of multiply genes involved in oxidation reduction and glucose metabolism detected in both species is consistent with metabolic suppression and lower energy demand in skeletal muscle during inactivity of hibernation. Black bears sampled during winter hibernation were compared with the animals sampled during summer. Muscle tissue were hybridized on a custom 12,800 cDNA probe nylon membrane microarray platform . Six hibernating and six summer active bears were studied in the experiment.

Project description:Hibernation is energy saving adaptation involving suppression of activity to survive in highly seasonal environments. Immobility and disuse generate muscle loss in most mammalian species. In contrast to other mammals, bears and ground squirrels demonstrate limited muscle atrophy over the physical inactivity of winter hibernation. This suggests that hibernating mammals have adaptive mechanisms to prevent disuse muscle atrophy. To identify common transcriptional program underlying molecular mechanisms preventing muscle loss, we conducted a large-scale gene expression screening in hind limb muscles comparing hibernating and summer active black bears and arctic ground squirrels by the use of custom 9,600 probe cDNA microarrays. The molecular pathway analysis showed an elevated proportion of overexpressed genes involved in all stages of protein biosynthesis and ribosome biogenesis in muscle of both species during hibernation that implies induction of translation at different hibernation states. The induction of protein biosynthesis likely contributes to attenuation of disuse muscle atrophy through prolonged periods of immobility and starvation. This adaptive mechanism allows hibernating mammals to maintain full musculoskeletal function and preserve mobility during and immediately after hibernation, thus promoting survival. The lack of directional changes in genes of protein catabolic pathways does not support the importance of metabolic suppression for preserving muscle mass during winter. Coordinated reduction of multiply genes involved in oxidation reduction and glucose metabolism detected in both species is consistent with metabolic suppression and lower energy demand in skeletal muscle during inactivity of hibernation. Arctic ground squirrels sampled during winter hibernation were compared with the animals sampled during summer. Muscle was hybridized on a custom 9,600 probes nylon membrane microarray platform. Ten in late torpor, four in early arousal, then in late arousal were studied in experiments.

Dataset Information

Proteogenomic analysis in hibernating mammal suggests contribution of skeletal muscle physiology to hibernation phenotype

Publications

Characterizing Cardiac Molecular Mechanisms of Mammalian Hibernation via Quantitative Proteogenomics.

Similar Datasets

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