Living in the Cold: Freeze‐induced Gene Responses in Freeze‐tolerant Vertebrates

Storey, Kenneth B.

doi:10.1046/j.1440-1681.1999.02990.x

Cited by 29 publications

(15 citation statements)

References 47 publications

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“…Natural freezing survival involves coordinated adjustments to metabolism to allow organisms to endure the multiple stresses (prominently including ischemia and cellular volume reduction) associated with the freezing of extracellular body fluids. Selected biochemical adaptations have been extensively studied (e.g., glucose use as a cryoprotectant; energy metabolism) (1,2), but the recent application of gene screening technology is allowing for the identification of other contributing factors (3,6). The present study describes the up‐regulation of a novel gene, li16 , during freezing and analyzes the influences on its expression.…”

Section: Discussionmentioning

confidence: 99%

Identification and characterization of a novel freezing‐inducible gene, li16, in the wood frog Rana sylvatica

McNally

Sturgeon

et al. 2002

FASEB j.

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The wood frog Rana sylvatica survives for weeks during winter hibernation with up to 65% body water frozen as ice. Natural freeze tolerance includes both seasonal and freeze-induced molecular adaptations that control ice formation, deal with long-term ischemia, regulate cell volume changes, and protect macromolecules. This report identifies and characterizes a novel freeze-inducible gene, li16, that codes for a protein of 115 amino acids. Northern blot analysis showed that li16 transcript levels rose quickly during freezing to reach levels 3.7-fold higher than control values after 24 h; immunoblotting showed a parallel 2.4-fold rise in Li16 protein. Regulatory influences on gene expression were assessed. Nuclear runoff assays confirmed that freezing initiated an increase in the rate of li16 transcription, and analysis of signal transduction pathways via in vitro incubation of liver slices implicated a cGMP-mediated pathway in li16 expression. Gene and protein expression in liver was also strongly stimulated by anoxia exposure, whereas the gene was less responsive to dehydration stress. The strong response of li16 to both freezing and anoxia, and the rapid down-regulation of the gene when oxygen was reintroduced, suggest that the Li16 protein may play a role in ischemia resistance during freezing.

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Section: Discussionmentioning

confidence: 99%

Identification and characterization of a novel freezing‐inducible gene, li16, in the wood frog Rana sylvatica

McNally

Sturgeon

et al. 2002

FASEB j.

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“…One of the most critical strategies for freeze tolerance involves the synthesis of high amounts of low-molecular-weight carbohydrates (glucose in wood frogs), which provide colligative resistance to detrimental decreases in cell volume while also serving to stabilize the phospholipid bilayer of membranes and to restrict the formation of intracellular ice [112-114]. Importantly, research has shown that simple augmentation strategies such as increasing endogenous levels of cryoprotectants (via injection) prior to freezing have the capacity to improve survival and extend the time in a frozen state in a certain context from 2 weeks to 49 days [113].…”

Section: High-subzero Preservationmentioning

confidence: 99%

New Approaches to Cryopreservation of Cells, Tissues, and Organs

Taylor¹,

Weegman²,

Baicu³

et al. 2019

Transfus Med Hemother

135

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In this concept article, we outline a variety of new approaches that have been conceived to address some of the remaining challenges for developing improved methods of biopreservation. This recognizes a true renaissance and variety of complimentary, high-potential approaches leveraging inspiration by nature, nanotechnology, the thermodynamics of pressure, and several other key fields. Development of an organ and tissue supply chain that can meet the healthcare demands of the 21st century means overcoming twin challenges of (1) having enough of these lifesaving resources and (2) having the means to store and transport them for a variety of applications. Each has distinct but overlapping logistical limitations affecting transplantation, regenerative medicine, and drug discovery, with challenges shared among major areas of biomedicine including tissue engineering, trauma care, transfusion medicine, and biomedical research. There are several approaches to biopreservation, the optimum choice of which is dictated by the nature and complexity of the tissue and the required length of storage. Short-term hypothermic storage at temperatures a few degrees above the freezing point has provided the basis for nearly all methods of preserving tissues and solid organs that, to date, have proved refractory to cryopreservation techniques successfully developed for single-cell systems. In essence, these short-term techniques have been based on designing solutions for cellular protection against the effects of warm and cold ischemia and basically rely upon the protective effects of reduced temperatures brought about by Arrhenius kinetics of chemical reactions. However, further optimization of such preservation strategies is now seen to be restricted. Long-term preservation calls for much lower temperatures and requires the tissue to withstand the rigors of heat and mass transfer during protocols designed to optimize cooling and warming in the presence of cryoprotective agents. It is now accepted that with current methods of cryopreservation, uncontrolled ice formation in structured tissues and organs at subzero temperatures is the single most critical factor that severely restricts the extent to which tissues can survive procedures involving freezing and thawing. In recent years, this major problem has been effectively circumvented in some tissues by using ice-free cryopreservation techniques based upon vitrification. Nevertheless, despite these promising advances there remain several recognized hurdles to be overcome before deep-subzero cryopreservation, either by classic freezing and thawing or by vitrification, can provide the much-needed means for biobanking complex tissues and organs for extended periods of weeks, months, or even years. In many cases, the approaches outlined here, including new underexplored paradigms of high-subzero preservation, are novel and inspired by mechanisms of freeze tolerance, or freeze avoidance, in nature. Others apply new bioengineering techniques such as nanotechnology, isochoric pressure preserv...

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“…Freezing imposes several challenges including: (A) physical stress as a result of ice crystal formation in the extracellular matrix and between organs which may be damaging to the architectural integrity of the cells and capillaries, (B) anoxic/ischemic stress to organs as a result of decrease in oxygen delivery due to blood plasma being frozen (C) dehydration stress as a result of losing up to ~60-70% of total body water to freezing resulting in organ dehydration and an increase in osmolality and ionic strength, and finally (D) physiological stress as a result of prolonged inactivity, complete cessation of heart beat, breathing, and brain activity (Storey, 1999;Storey & Storey 2004a, 2004b. Furthermore, these organisms have to also deal with challenges associated with thawing such as a large influx of reactive oxygen species upon oxygen reperfusion, cellular rehydration, and disuse of skeletal muscles during prolonged periods of inactivity.…”

Section: Adaptations To Sub-zero Temperaturesmentioning

confidence: 99%

“…In fact, the same study showed that wood frogs that hibernate in damp hibernacula lose only 2.5% of their total body water to evaporation while those that hibernate without covers will lose ~50% of their total body water in the same period of freezing (Churchill & Storey, 1993). Dehydration provides great benefits for wood frogs during freezing, it limits the amount of free water available and attenuates ice growth within the organs, thereby preventing intracellular ice formation (Storey, 1999). Wood frogs confine ice growth within the extra-organ space, abdominal cavity, the bladder, and/or between the skeletal muscle and the skin thus limiting cellular damage to tissues and capillaries (Storey, 1999).…”

Section: 5anoxia and Dehydrationmentioning

confidence: 99%

“…Dehydration provides great benefits for wood frogs during freezing, it limits the amount of free water available and attenuates ice growth within the organs, thereby preventing intracellular ice formation (Storey, 1999). Wood frogs confine ice growth within the extra-organ space, abdominal cavity, the bladder, and/or between the skeletal muscle and the skin thus limiting cellular damage to tissues and capillaries (Storey, 1999). In addition, during dehydration water is withdrawn from inside the cell to the extracellular matrix resulting in the increase of cryoprotectant glucose concentration inside the cell which would allow for better cellular protection (Storey, 1999;Storey & Storey, 2004a).…”

Section: 5anoxia and Dehydrationmentioning

confidence: 99%

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Regulation of the Nuclear Factor of Activated T Cell (NFAT) Family of Transcription Factors in the Freeze Tolerant Wood Frog, Rana sylvatica

Al-attar¹

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During winter, wood frogs (Rana sylvatica) can endure whole body freezing with 65-70% of total body water converted to extracellular ice. As a result, cells experience extensive dehydration when water exits as well as anoxia due to interruption of blood flow.Adapting to such challenges requires metabolic rearrangement, partially mediated by transcription factor control over gene expression. Here, involvement of the nuclear factor of activated T-cells (NFAT) transcription factors, isoforms c1-c4, was analyzed in liver and skeletal muscle over freeze/thaw and anoxia/re-oxygenation cycles. Freezing activated NFATc3 in liver, leading to increased osteopontin expression and glycogen synthase kinase 3β repression (the latter potentially linked with glucose production as a cryoprotectant). Anoxia activated NFATc4 in liver, leading to increased atrial natriuretic peptide levels. Neither freezing nor anoxia significantly affected NFATs in skeletal muscle.

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Living in the Cold: Freeze‐induced Gene Responses in Freeze‐tolerant Vertebrates

Cited by 29 publications

References 47 publications

Identification and characterization of a novel freezing‐inducible gene, li16, in the wood frog Rana sylvatica

Identification and characterization of a novel freezing‐inducible gene, li16, in the wood frog Rana sylvatica

New Approaches to Cryopreservation of Cells, Tissues, and Organs

Regulation of the Nuclear Factor of Activated T Cell (NFAT) Family of Transcription Factors in the Freeze Tolerant Wood Frog, Rana sylvatica

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