Digital transcriptome analysis indicates adaptive mechanisms in the heart of a hibernating mammal

2005 ◽  
Vol 23 (2) ◽  
pp. 227-234 ◽  
Author(s):  
Katharine M. Brauch ◽  
Nirish D. Dhruv ◽  
Eric A. Hanse ◽  
Matthew T. Andrews
Keyword(s):  
High Throughput Sequencing ◽  
Digital Gene Expression ◽  
Ground Squirrels ◽  
Pyruvate Dehydrogenase Kinase ◽  
Cdna Libraries ◽  
Body Temperatures ◽  
Triacylglycerol Lipase ◽  
Plasmic Reticulum ◽  
Comprehensive Survey ◽  
Dependent Protein

Survival of near-freezing body temperatures and reduced blood flow during hibernation is likely the result of changes in the expression of specific genes. In this study, we described a comprehensive survey of mRNAs in the heart of the thirteen-lined ground squirrel ( Spermophilus tridecemlineatus) before and during hibernation. The heart was chosen for this study because it is a contractile organ that must continue to work despite body temperatures of 5°C and the lack of food for periods of 5–6 mo. We used a digital gene expression assay involving high-throughput sequencing of directional cDNA libraries from hearts of active and hibernating ground squirrels to determine the identity and frequency of 3,532 expressed sequence tags (ESTs). Statistical analysis of the active and hibernating heart expression profile indicated the differential regulation of 48 genes based on a P ≤ 0.03 threshold. Several of the differentially expressed genes identified in this screen encode proteins that likely account for uninterrupted cardiac function during hibernation, including those involved in metabolism, contractility, Ca2+ handling, and low-temperature catalysis. A sampling of genes showing higher expression during hibernation includes phosphofructokinase, pancreatic triacylglycerol lipase, pyruvate dehydrogenase kinase 4 (PDK4), aldolase A, sarco(endo)plasmic reticulum Ca2+-ATPase 2a (SERCA2a), titin, and four-and-a-half LIM domains protein 2 (FHL2). Genes showing reduced levels of expression during hibernation include cyclin-dependent kinase 2-associated protein 1 (CDK2AP1), troponin C, phospholamban, Ca2+/calmodulin-dependent protein kinase II (CaMKII), calmodulin, and four subunits of cytochrome c oxidase.

Genes controlling the metabolic switch in hibernating mammals

2004 ◽  
Vol 32 (6) ◽  
pp. 1021-1024 ◽  
Author(s):  
M.T. Andrews
Keyword(s):  
Low Temperature ◽  
Pyruvate Dehydrogenase ◽  
Ground Squirrel ◽  
Mammalian Cells ◽  
Lipolytic Activity ◽  
Tricarboxylic Acid Cycle ◽  
Ground Squirrels ◽  
Pyruvate Dehydrogenase Kinase ◽  
Body Temperatures ◽  
Triacylglycerol Lipase

Hibernating mammals have the ability to decrease their metabolic rate and survive up to 6 months without food in an inactive state where body temperatures approach 0°C. In hibernating 13-lined ground squirrels (Spermophilus tridecemlineatus), oxygen consumption holds at 1/30 to 1/50 of the aroused condition and heart rates are as low as 3–10 beats/min, compared with 200–300 beats/min when the animal is active. This seasonal adaptation requires a metabolic shift away from the oxidation of carbohydrates and towards the combustion of stored fatty acids as the primary source of energy. A key element in this fuel switch is the differential expression of the gene encoding pyruvate dehydrogenase kinase isoenzyme 4. Pyruvate dehydrogenase kinase isoenzyme 4 inhibits pyruvate dehydrogenase and thus minimizes carbohydrate oxidation by preventing the flow of glycolytic products into the tricarboxylic acid cycle. Hibernators also exploit the low-temperature activity of PTL (pancreatic triacylglycerol lipase) in both heart and white adipose tissue. Lipolytic activity at body temperatures associated with hibernation was examined using recombinant ground squirrel and human PTL expressed in yeast. Enzymes from both humans and ground squirrel displayed high activity at temperatures as low as 0°C and showed Q10=1.2–1.5 over the temperature range 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.

Parasympathetic influence on heart rate in euthermic and hibernating ground squirrels.

1995 ◽  
Vol 198 (4) ◽  
pp. 931-937 ◽  
Author(s):  
M B Harris ◽  
W K Milsom
Keyword(s):  
Heart Rate ◽  
Ambient Temperature ◽  
Parasympathetic Nervous System ◽  
Ground Squirrels ◽  
Relative Role ◽  
Body Temperatures ◽  
Inotropic Effects ◽  
Ambient Temperatures ◽  
Isolated Hearts ◽  
C 32

The relative role of the parasympathetic nervous system during deep hibernation is enigmatic. Conflicting hypotheses exist, and both sides draw support from investigations of vagal influence on the heart. Recent studies have shown cardiac chronotropic and inotropic effects of parasympathetic stimulation and inhibition in isolated hearts and anesthetized animals at hibernating body temperatures. No studies, however, have demonstrated such occurrences in undisturbed deeply hibernating animals. The present study documents respiratory-related alterations in heart rate during euthermia and hibernation at ambient temperatures of 15, 10 and 5 degrees C mediated by parasympathetic influence. During quiet wakefulness, euthermic squirrels breathed continuously and exhibited a 29% acceleration in heart rate during inspiration. During deep undisturbed hibernation, at 15, 10 and 5 degrees C ambient temperature, animals exhibited an episodic breathing pattern and body temperatures were slightly above ambient temperature. At each temperature, heart rate during the respiratory episode was greater than that during the apnea. The magnitude of this ventilatory tachycardia decreased with ambient temperature, being 108% at 15 degrees C, 32% at 10 degrees C and 11.5% at 5 degrees C. Animals exposed to 3% CO2 at 5 degrees C, which significantly increased ventilation, still exhibited an 11.7% increase in heart rate during breathing. Thus, the magnitude of the ventilation tachycardia was independent of the level of ventilation, at least over the range studied. Inhibition of vagus nerve conduction at 5 degrees C was achieved using localized nerve block. This led to an increase in apneic heart rate and abolished the ventilatory tachycardia.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Genome-Wide Analysis and Function Prediction of Long Noncoding RNAs in Sheep Pituitary Gland Associated with Sexual Maturation

Genes ◽  
2020 ◽  
Vol 11 (3) ◽  
pp. 320
Author(s):  
Hua Yang ◽  
Jianyu Ma ◽  
Zhibo Wang ◽  
Xiaolei Yao ◽  
Jie Zhao ◽  
...  
Keyword(s):  
Pituitary Gland ◽  
Sexual Maturation ◽  
Noncoding Rna ◽  
High Throughput Sequencing ◽  
Male Reproduction ◽  
Functional Enrichment ◽  
Cdna Libraries ◽  
Pituitary Cells ◽  
Hpt Axis ◽  
Male Sheep

Long noncoding RNA (lncRNA) plays a crucial role in the hypothalamic-pituitary-testis (HPT) axis associated with sheep reproduction. The pituitary plays a connecting role in the HPT axis. However, little is known of their expression pattern and potential roles in the pituitary gland. To explore the potential lncRNAs that regulate the male sheep pituitary development and sexual maturation, we constructed immature and mature sheep pituitary cDNA libraries (three-month-old, TM, and nine-month-old, NM, respectively, n = 3) for lncRNA and mRNA high-throughput sequencing. Firstly, the expression of lncRNA and mRNA were comparatively analyzed. 2417 known lncRNAs and 1256 new lncRNAs were identified. Then, 193 differentially expressed (DE) lncRNAs and 1407 DE mRNAs were found in the pituitary between the two groups. Moreover, mRNA-lncRNA interaction network was constructed according to the target gene prediction of lncRNA and functional enrichment analysis. Five candidate lncRNAs and their targeted genes HSD17B12, DCBLD2, PDPK1, GPX3 and DLL1 that enriched in growth and reproduction related pathways were further filtered. Lastly, the interaction of candidate lncRNA TCONS_00066406 and its targeted gene HSD17B12 were validated in in vitro of sheep pituitary cells. Our study provided a systematic presentation of lncRNAs and mRNAs in male sheep pituitary, which revealed the potential role of lncRNA in male reproduction.

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

2003 ◽  
Vol 16 (1) ◽  
pp. 131-140 ◽  
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.

scholarly journals Systematic Survey of the Alteration of the Faecal Microbiota in Rats With Gastrointestinal Disorder and Modulation by Multicomponent Drugs

2021 ◽  
Vol 12 ◽  
Author(s):  
Yue Wu ◽  
Yang Wu ◽  
Hongwei Wu ◽  
Changxun Wu ◽  
Enhui Ji ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
High Throughput Sequencing ◽  
Intestinal Flora ◽  
Ether Lipid ◽  
Gastrointestinal Disorder ◽  
Systematic Evaluation ◽  
Faecal Microbiota ◽  
Sequencing Strategy ◽  
Comprehensive Survey ◽  
Medical Burden

Gastrointestinal disorder (GID) is a global health disease which leads to heavy public medical burden. Disorders in the intestinal flora have been found in gastrointestinal disorder patients. However, the interaction between GID and the intestinal flora in faecal has not been studied comprehensively. In addition, multicomponent drugs represented by traditional Chinese medicine (TCM) are widely used for treating GID, but their modulation of the intestinal flora has not been investigated. Therefore, in this study, a high-throughput sequencing strategy was used to investigate alterations in the intestinal flora in a rat GID model, followed by an investigation of the modulation by a representative TCM, Xiaoerfupi (XEFP) granule. The results showed that in rats with GID, the relative abundances of Erysipelotrichaceae, Lachnospiraceae, Streptococcaceae increased and that of Ruminococcaceae decreased. At the macro level, the levels of LysoPC(16:0), LysoPC(20:2), LysoPC(15:0), LysoPC(20:2 (11Z, 14Z)), LysoPC(20:1), LysoPC(15:0), LysoPC(20:0) and LysoPE (0:0/20:0) in serum increased and levels of PC(36:4), PC(38:4), PC(o-36;4), PE (MonoMe(13,5)/MonoMe(11,5)) decreased. The imbalance of metabolites was restored by XEFP through ether lipid metabolism pathway. Increase in the phyla Firmicutes/Bacteroidetes (F/B) ratio of the GID rats was restored by XEFP as well. Moreover, XEFP can relief the symptoms of GID rats by increasing bacteria Ruminococcaceae and decreasing Streptococcaceae, Erysipelotrichaceae and Lachnospiraceae in faecal microbiota level. This study represents a comprehensive survey of the interaction between GID and the intestinal flora and a systematic evaluation of modulation by a multicomponent drug.

Survival time of hypothermic white rats (15°C) and ground squirrels (10°C)

1960 ◽  
Vol 199 (3) ◽  
pp. 463-466 ◽  
Author(s):  
V. Popovic
Keyword(s):  
Body Temperature ◽  
Survival Time ◽  
Ground Squirrels ◽  
Sodium Pentobarbital ◽  
Body Temperatures ◽  
Survival Times ◽  
Young Rats ◽  
White Rats

The survival times of intensively cooled white rats decrease with their body temperatures. When cooled by Giaja's technique and maintained afterwards at a body temperature of 15°C rats survived 9 hours, but they could be revived by rewarming only during the first 5.5 hours of survival (biological survival). Similar biological survival times were found when the rats were cooled by other techniques, whether the cooling was much quicker or much slower. The survival time was also independent of the rate of rewarming from hypothermia. Survival was shortened by cooling after administration of sodium pentobarbital. Biological survival of young 40-gm rats at 15°C body temperature was 19 hours, 14 hours longer than that of hypothermic adults. Level of O2 consumption of hypothermic young rats differed from those of hypothermic adult animals.

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