Myosin Isoform Expression and MAFbx mRNA Levels in Hibernating Golden‐Mantled Ground Squirrels (Spermophilus lateralis)

Hibernators in torpor dramatically reduce their metabolic, respiratory, and heart rates and core body temperature. These extreme physiological conditions are frequently and rapidly reversed during the winter hibernation season via endogenous mechanisms. This phenotype must derive from regulated expression of the hibernator’s genome; to identify its molecular components, a cDNA subtraction was used to enrich for seasonally upregulated mRNAs in liver of golden-mantled ground squirrels. The relative steady-state levels for seven mRNAs identified by this screen, plus five others, were measured and analyzed for seasonal and stage-specific differences using kinetic RT-PCR. Four mRNAs show seasonal upregulation in which all five winter stages differ significantly from and are higher than summer (α2-macroglobulin, apolipoprotein A1, cathepsin H, and thyroxine-binding globulin). One of these mRNAs, α2-macroglobulin, varies during the winter stages with significantly lower levels at late torpor. None of the 12 mRNAs increased during torpor. The implications for these newly recognized upregulated mRNAs for hibernation as well as more global issues of maintaining steady-state levels of mRNA during torpor are discussed.

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DDR1 methylation is associated with bipolar disorder and the isoform expression and methylation of myelin genes

Epigenomics ◽

10.2217/epi-2021-0006 ◽

2021 ◽

Author(s):

Beatriz Garcia-Ruiz ◽

Manuel Castro de Moura ◽

Gerard Muntané ◽

Lourdes Martorell ◽

Elena Bosch ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Bipolar Disorder ◽

Mrna Expression ◽

Gene Expression Analysis ◽

Mrna Levels ◽

Healthy Controls ◽

Genome Wide ◽

Isoform Expression

Aim: To investigate DDR1 methylation in the brains of bipolar disorder (BD) patients and its association with DDR1 mRNA levels and comethylation with myelin genes. Materials & methods: Genome-wide profiling of DNA methylation (Infinium MethylationEPIC BeadChip) corrected for glial composition and DDR1 gene expression analysis in the occipital cortices of individuals with BD (n = 15) and healthy controls (n = 15) were conducted. Results: DDR1 5-methylcytosine levels were increased and directly associated with DDR1b mRNA expression in the brains of BD patients. We also observed that DDR1 was comethylated with a group of myelin genes. Conclusion: DDR1 is hypermethylated in BD brain tissue and is associated with isoform expression. Additionally, DDR1 comethylation with myelin genes supports the role of this receptor in myelination.

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Bone strength is maintained after 8 months of inactivity in hibernating ground squirrels, Spermophilus lateralis

The FASEB Journal ◽

10.1096/fasebj.22.1_supplement.757.33 ◽

2008 ◽

Vol 22 (S1) ◽

Author(s):

Jenifer C. Utz ◽

Stacy Nelson ◽

Brendan J. O'toole ◽

Frank Breukelen

Keyword(s):

Bone Strength ◽

Ground Squirrels ◽

Spermophilus Lateralis

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Modulation of gene expression in hibernating arctic ground squirrels

Physiological Genomics ◽

10.1152/physiolgenomics.00075.2007 ◽

2008 ◽

Vol 32 (2) ◽

pp. 170-181 ◽

Cited By ~ 100

Author(s):

Jun Yan ◽

Brian M. Barnes ◽

Franziska Kohl ◽

Thomas G. Marr

Keyword(s):

Gene Expression ◽

Circadian Rhythm ◽

Cell Growth ◽

Acid Metabolism ◽

Molecular Transport ◽

Ground Squirrels ◽

Mrna Levels ◽

Brown Adipose ◽

Modulation Of Gene Expression ◽

Arctic Ground Squirrels

We performed a broadscale screening of differential gene expression using both high-throughput bead-array technology and real-time PCR assay in brown adipose tissue, liver, heart, hypothalamus, and skeletal muscle in hibernating arctic ground squirrels, comparing animals sampled after two durations of steady-state torpor, during two stages of spontaneous arousal episodes, and in animals after they ended hibernation. Significant seasonal and torpor-arousal cycle differences of gene expression were detected in genes involved in glycolysis, fatty acid metabolism, gluconeogenesis, amino acid metabolism, molecular transport, detoxification, cardiac contractility, circadian rhythm, cell growth and apoptosis, muscle dystrophy, and RNA and protein protection. We observed, for the first time, complex modulation of gene expression during multiple stages of torpor-arousal cycles. The mRNA levels of certain metabolic genes drop significantly during the transition from late torpor to early arousal, perhaps due to the rapid turnover of mRNA transcripts resulting from the translational demands during thermogenesis in early arousal, whereas the mRNA levels of genes related to circadian rhythm, cell growth, and apoptosis rise significantly in the early or late arousal phases during torpor-arousal cycle, suggesting the resumption of circadian rhythm and cell cycle during arousal.

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Are ground squirrels sleep deprived during hibernation?

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1991.260.6.r1123 ◽

1991 ◽

Vol 260 (6) ◽

pp. R1123-R1129 ◽

Cited By ~ 19

Author(s):

L. Trachsel ◽

D. M. Edgar ◽

H. C. Heller

Keyword(s):

Slow Wave ◽

Slow Wave Sleep ◽

Ground Squirrels ◽

Wave Intensity ◽

Spermophilus Lateralis ◽

Sleep Debt ◽

Function Of Sleep ◽

Deep Hibernation ◽

To Receive ◽

Periodic Arousals

Hibernation is an adaptation for energy conservation, which probably evolved as an extension of non-rapid-eye-movement sleep mechanisms. Yet, during periodic arousals from bouts of deep hibernation, ground squirrels (Spermophilus lateralis) spend most of their time asleep. Spectral analysis of the electroencephalogram revealed that cortical slow-wave intensity during sleep is high at the beginning of a euthermic period and declines thereafter. Sleep slow-wave intensity is greater after longer bouts of hibernation than after shorter bouts. We hypothesize that low body temperatures during hibernation are incompatible with the restorative function of sleep as reflected in cortical slow-wave activity. Animals must incur the energetic costs of periodic arousals from hibernation to receive the restorative benefits of euthermic slow-wave sleep. The timing of arousals from hibernation may be a function of accumulated sleep debt.

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Pancreatic triacylglycerol lipase in a hibernating mammal. II. Cold-adapted function and differential expression

Physiological Genomics ◽

10.1152/physiolgenomics.00168.2002 ◽

2003 ◽

Vol 16 (1) ◽

pp. 131-140 ◽

Cited By ~ 22

Author(s):

Teresa L. Squire ◽

Mark E. Lowe ◽

Vernon W. Bauer ◽

Matthew T. Andrews

Keyword(s):

Low Temperature ◽

High Activity ◽

Ground Squirrel ◽

Mammalian Cells ◽

Lipolytic Activity ◽

Tissue Expression ◽

Ground Squirrels ◽

Mrna Levels ◽

Western Blots ◽

Triacylglycerol Lipase

Thirteen-lined ground squirrels ( Spermophilus tridecemlineatus) exploit the low-temperature activity of pancreatic triacylglycerol lipase (PTL) during hibernation. Lipolytic activity at body temperatures associated with hibernation was examined using recombinant ground squirrel and human PTLs expressed in yeast. Both the human and ground squirrel enzymes displayed high activity at temperatures as low as 0°C and showed Q10 values of 1.2–1.5 over a range of 37–7°C. These studies indicate that low-temperature lipolysis is a general property of PTL and does not require protein modifications unique to mammalian cells and/or the hibernating state. Western blots show elevated levels of PTL protein during hibernation in both heart and white adipose tissue (WAT). Significant increases in PTL gene expression are seen in heart, WAT, and testes; but not in pancreas, where PTL mRNA levels are highest. Upregulation of PTL in testes is also accompanied by expression of the PTL-specific cofactor, colipase. The multi-tissue expression of PTL during hibernation supports its role as a key enzyme that shows high activity at low temperatures.

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Circannual and Seasonal Variations in Plasma Luteinizing Hormone Levels of Ovariectomized Ground Squirrels (Spermophilus lateralis)

Biology of Reproduction ◽

10.1095/biolreprod28.1.178 ◽

1983 ◽

Vol 28 (1) ◽

pp. 178-185 ◽

Cited By ~ 10

Author(s):

Irving Zucker ◽

Paul Licht

Keyword(s):

Luteinizing Hormone ◽

Seasonal Variations ◽

Ground Squirrels ◽

Hormone Levels ◽

Spermophilus Lateralis

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Different effects on human skeletal myosin heavy chain isoform expression: strength vs. combination training

Journal of Applied Physiology ◽

10.1152/japplphysiol.00830.2002 ◽

2003 ◽

Vol 94 (6) ◽

pp. 2282-2288 ◽

Cited By ~ 56

Author(s):

Y. Liu ◽

A. Schlumberger ◽

K. Wirth ◽

D. Schmidtbleicher ◽

J. M. Steinacker

Keyword(s):

Strength Training ◽

Myosin Heavy Chain ◽

Heavy Chain ◽

Mrna Levels ◽

Triceps Brachii ◽

Myosin Heavy Chain Isoform ◽

Before And After ◽

Skeletal Myosin ◽

Isoform Expression ◽

Significant Change

Myosin heavy chain (MHC) isoform expression changes with physical training. This may be one of the mechanisms for muscular adaptation to exercise. We aimed to investigate the effects of different strength-training protocols on MHC isoform expression, bearing in mind that α- MHCslow(newly identified MHC isoform) mRNA may be upregulated in response to training. Twelve volunteers performed a 6-wk strength training with maximum contractions (Max group), and another 12 of similar age performed combination training of maximum contractions and ballistic and stretch-shortening movements (Combi group). Muscle samples were taken from triceps brachii before and after training. MHC isoform composition was determined by SDS-PAGE silver staining, and mRNA levels of MHC isoforms were determined by RT-PCR. In Max group, there was an increase in MHC2A (49.4 to 66.7%, P< 0.01) and a decrease in MHC2X (33.4 to 19.5%, P < 0.01) after training, although there was no significant change in MHCslow. In Combi group, there was also an increase in MHC2A (47.7 to 62.7%, P < 0.05) and a decrease in MHCslow (18.2 to 9.2%, P < 0.05) but no significant change in MHC2X. An upregulation of α-MHCslow mRNA was, therefore, found in both groups as a result of training. The strength training with maximum contractions led to a shift in MHC isoform composition from 2X to 2A, whereas the combined strength training produced an MHC isoform composition shift from slow to 2A.

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