Red Blood Cell Metabolic Responses to Torpor and Arousal in the Hibernator Arctic Ground Squirrel
Arctic ground squirrels provide a unique model to investigate metabolic responses to hibernation in mammals. During winter months these rodents are exposed to severe hypothermia, prolonged fasting, and hypoxemia. In the light of their role in oxygen transport/off-loading and owing to the absence of...
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ftpubmed:oai:pubmedcentral.nih.gov:7219541 2023-05-15T14:31:30+02:00 Red Blood Cell Metabolic Responses to Torpor and Arousal in the Hibernator Arctic Ground Squirrel Gehrke, Sarah Rice, Sarah Stefanoni, Davide Wilkerson, Rebecca B. Nemkov, Travis Reisz, Julie A. Hansen, Kirk C. Lucas, Alfredo Cabrales, Pedro Drew, Kelly Alessandro, Angelo D’ 2019-02-28 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7219541/ http://www.ncbi.nlm.nih.gov/pubmed/30793910 https://doi.org/10.1021/acs.jproteome.9b00018 en eng http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7219541/ http://www.ncbi.nlm.nih.gov/pubmed/30793910 http://dx.doi.org/10.1021/acs.jproteome.9b00018 J Proteome Res Article Text 2019 ftpubmed https://doi.org/10.1021/acs.jproteome.9b00018 2020-05-17T00:40:40Z Arctic ground squirrels provide a unique model to investigate metabolic responses to hibernation in mammals. During winter months these rodents are exposed to severe hypothermia, prolonged fasting, and hypoxemia. In the light of their role in oxygen transport/off-loading and owing to the absence of nuclei and organelles (and thus de novo protein synthesis capacity), mature red blood cells have evolved metabolic programs to counteract physiological or pathological hypoxemia. However, red blood cell metabolism in hibernation has not yet been investigated. Here we employed targeted and untargeted metabolomics approaches to investigate erythrocyte metabolism during entrance to torpor to arousal, with a high resolution of the intermediate time points. We report that torpor and arousal promote metabolism through glycolysis and pentose phosphate pathway, respectively, consistent with previous models of oxygen-dependent metabolic modulation in mature erythrocytes. Erythrocytes from hibernating squirrels showed up to 100-fold lower levels of biomarkers of reperfusion injury, such as the pro-inflammatory dicarboxylate succinate. Altered tryptophan metabolism during torpor was here correlated to the accumulation of potentially neurotoxic catabolites kynurenine, quinolinate, and picolinate. Arousal was accompanied by alterations of sulfur metabolism, including sudden spikes in a metabolite putatively identified as thiorphan (level 1 confidence) —a potent inhibitor of several metalloproteases that play a crucial role in nociception and inflammatory complication to reperfusion secondary to ischemia or hemorrhage. Preliminary studies in rats showed that intravenous injection of thiorphan prior to resuscitation mitigates metabolic and cytokine markers of reperfusion injury, etiological contributors to inflammatory complications after shock. Text Arctic ground squirrel Arctic PubMed Central (PMC) Arctic Journal of Proteome Research 18 4 1827 1841 |
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Article Gehrke, Sarah Rice, Sarah Stefanoni, Davide Wilkerson, Rebecca B. Nemkov, Travis Reisz, Julie A. Hansen, Kirk C. Lucas, Alfredo Cabrales, Pedro Drew, Kelly Alessandro, Angelo D’ Red Blood Cell Metabolic Responses to Torpor and Arousal in the Hibernator Arctic Ground Squirrel |
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Article |
description |
Arctic ground squirrels provide a unique model to investigate metabolic responses to hibernation in mammals. During winter months these rodents are exposed to severe hypothermia, prolonged fasting, and hypoxemia. In the light of their role in oxygen transport/off-loading and owing to the absence of nuclei and organelles (and thus de novo protein synthesis capacity), mature red blood cells have evolved metabolic programs to counteract physiological or pathological hypoxemia. However, red blood cell metabolism in hibernation has not yet been investigated. Here we employed targeted and untargeted metabolomics approaches to investigate erythrocyte metabolism during entrance to torpor to arousal, with a high resolution of the intermediate time points. We report that torpor and arousal promote metabolism through glycolysis and pentose phosphate pathway, respectively, consistent with previous models of oxygen-dependent metabolic modulation in mature erythrocytes. Erythrocytes from hibernating squirrels showed up to 100-fold lower levels of biomarkers of reperfusion injury, such as the pro-inflammatory dicarboxylate succinate. Altered tryptophan metabolism during torpor was here correlated to the accumulation of potentially neurotoxic catabolites kynurenine, quinolinate, and picolinate. Arousal was accompanied by alterations of sulfur metabolism, including sudden spikes in a metabolite putatively identified as thiorphan (level 1 confidence) —a potent inhibitor of several metalloproteases that play a crucial role in nociception and inflammatory complication to reperfusion secondary to ischemia or hemorrhage. Preliminary studies in rats showed that intravenous injection of thiorphan prior to resuscitation mitigates metabolic and cytokine markers of reperfusion injury, etiological contributors to inflammatory complications after shock. |
format |
Text |
author |
Gehrke, Sarah Rice, Sarah Stefanoni, Davide Wilkerson, Rebecca B. Nemkov, Travis Reisz, Julie A. Hansen, Kirk C. Lucas, Alfredo Cabrales, Pedro Drew, Kelly Alessandro, Angelo D’ |
author_facet |
Gehrke, Sarah Rice, Sarah Stefanoni, Davide Wilkerson, Rebecca B. Nemkov, Travis Reisz, Julie A. Hansen, Kirk C. Lucas, Alfredo Cabrales, Pedro Drew, Kelly Alessandro, Angelo D’ |
author_sort |
Gehrke, Sarah |
title |
Red Blood Cell Metabolic Responses to Torpor and Arousal in the Hibernator Arctic Ground Squirrel |
title_short |
Red Blood Cell Metabolic Responses to Torpor and Arousal in the Hibernator Arctic Ground Squirrel |
title_full |
Red Blood Cell Metabolic Responses to Torpor and Arousal in the Hibernator Arctic Ground Squirrel |
title_fullStr |
Red Blood Cell Metabolic Responses to Torpor and Arousal in the Hibernator Arctic Ground Squirrel |
title_full_unstemmed |
Red Blood Cell Metabolic Responses to Torpor and Arousal in the Hibernator Arctic Ground Squirrel |
title_sort |
red blood cell metabolic responses to torpor and arousal in the hibernator arctic ground squirrel |
publishDate |
2019 |
url |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7219541/ http://www.ncbi.nlm.nih.gov/pubmed/30793910 https://doi.org/10.1021/acs.jproteome.9b00018 |
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Arctic |
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Arctic |
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Arctic ground squirrel Arctic |
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Arctic ground squirrel Arctic |
op_source |
J Proteome Res |
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7219541/ http://www.ncbi.nlm.nih.gov/pubmed/30793910 http://dx.doi.org/10.1021/acs.jproteome.9b00018 |
op_doi |
https://doi.org/10.1021/acs.jproteome.9b00018 |
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Journal of Proteome Research |
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18 |
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4 |
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1827 |
op_container_end_page |
1841 |
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1766305110969810944 |