Role of MicroRNAs in Extreme Animal Survival Strategies.

The critical role microRNAs play in modulating global functions is emerging, both in the maintenance of homeostatic mechanisms and in the adaptation to diverse environmental stresses. When stressed, cells must divert metabolic requirements toward immediate survival and eventual recovery and the unique features of miRNAs, such as their relatively ATP-inexpensive biogenesis costs, and the quick and reversible nature of their action, renders them excellent "master controllers" for rapid responses. Many animal survival strategies for dealing with extreme environmental pressures involve prolonged retreats into states of suspended animation to extend the time that they can survive on their limited internal fuel reserves until conditions improve.

Insights from a vertebrate model organism on the molecular mechanisms of whole-body dehydration tolerance.

Studies on the molecular mechanisms of dehydration tolerance have been largely limited to plants and invertebrates. Currently, research in whole body dehydration of complex animals is limited to cognitive and behavioral effects in humans, leaving the molecular mechanisms of vertebrate dehydration relatively unexplored. The present review summarizes studies to date on the African clawed frog (Xenopus laevis) and examines whole-body dehydration on physiological, cellular and molecular levels.

Phosphoproteomic Analysis of Reveals Expression and Phosphorylation of Hypoxia-Inducible PFKFB3 during Dehydration.

tolerate dehydration when their environments evaporate during summer months. Protein phosphorylation has previously shown to regulate important adaptations in , including the transition to anaerobic metabolism. We therefore performed phosphoproteomic analysis of to further elucidate the cellular and metabolic responses to dehydration.

MicroRNA expression in the heart of Xenopus laevis facilitates metabolic adaptation to dehydration.

Xenopus laevis survive severe dehydration during the summer months in their natural range. MicroRNA regulate translation of target mRNAs and have shown to be differentially expressed in response to dehydration in X. laevis.

Advances and applications of environmental stress adaptation research.

Evolution has produced animals that survive extreme fluctuations in environmental conditions including freezing temperatures, anoxia, desiccating conditions, and prolonged periods without food. For example, the wood frog survives whole-body freezing every winter, arresting all gross physiological functions, but recovers functions upon thawing in the spring. Likewise, many small mammals hibernate for months at a time with minimal metabolic activity, organ perfusion, and movement, yet do not suffer significant muscle atrophy upon arousal.

Naked mole rats activate neuroprotective proteins during hypoxia.

Naked mole rats are a long-lived animal model that age much like humans, but that can also withstand oxidative damage, cancer, neurodegenerative diseases, and severe hypoxic conditions, which is of particular interest to this study. The conditions of their underground burrows result in competition for oxygen consumption, yet despite this oxygen deprivation they emerge unscathed. To understand the mechanisms in place to facilitate neuronal preservation during hypoxia, we investigated the protein levels of well-known cell-stress factors.

DNA methylation and regulation of DNA methyltransferases in a freeze-tolerant vertebrate.

The wood frog is one of the few freeze-tolerance vertebrates. This is accomplished in part by the accumulation of cryoprotectant glucose, metabolic rate depression, and stress response activation. These may be achieved by mechanisms such as DNA methylation, which is typically associated with transcriptional repression.

Glucose and urea metabolic enzymes are differentially phosphorylated during freezing, anoxia, and dehydration exposures in a freeze tolerant frog.

Vertebrate freeze tolerance requires multiple adaptations underpinned by specialized biochemistry. Freezing of extracellular water leads to intracellular dehydration as pure water is incorporated into growing ice crystals and also results in the cessation of blood supply to tissues, creating an anoxic cellular environment. Hence, the freeze tolerant wood frog, Rana sylvatica, must endure both dehydration and anoxia stresses in addition to freezing.

Transcriptional regulation of metabolism in disease: From transcription factors to epigenetics.

Every cell in an individual has largely the same genomic sequence and yet cells in different tissues can present widely different phenotypes. This variation arises because each cell expresses a specific subset of genomic instructions. Control over which instructions, or genes, are expressed is largely controlled by transcriptional regulatory pathways.

Roles for lysine acetyltransferases during mammalian hibernation.

The thirteen-lined ground squirrel (Ictidomys tridecemlineatus) is a well-known model for studying hibernation. While in a torpid state, these animals globally suppress energy expensive processes, while supporting specialized pathways necessary for survival. Lysine acetyltransferases (KATs) play a crucial role in modulating the expression and activity of a wide-variety of cellular pathways and processes, and therefore, may play a role during hibernation when the cell is shifting to an energy conservative, cytoprotective state.

Dynamic regulation of six histone H3 lysine (K) methyltransferases in response to prolonged anoxia exposure in a freshwater turtle.

The importance of histone lysine methylation is well established in health, disease, early development, aging, and cancer. However, the potential role of histone H3 methylation in regulating gene expression in response to extended periods of oxygen deprivation (anoxia) in a natural, anoxia-tolerant model system is underexplored. Red-eared sliders (Trachemys scripta elegans) can tolerate and survive three months of absolute anoxia and recover without incurring detrimental cellular damage, mainly by reducing the overall metabolic rate by 90% when compared to normoxia.

Improved high-throughput quantification of luminescent microplate assays using a common Western-blot imaging system.

Common Western-blot imaging systems have previously been adapted to measure signals from luminescent microplate assays. This can be a cost saving measure as Western-blot imaging systems are common laboratory equipment and could substitute a dedicated luminometer if one is not otherwise available. One previously unrecognized limitation is that the signals captured by the cameras in these systems are not equal for all wells.

Histone methylation in the freeze-tolerant wood frog (Rana sylvatica).

Freeze-tolerant animals survive sub-zero temperatures and long-term starvation associated with the winter by lowering their metabolic rate using a variety of transcriptional, translational, and post-translational regulatory methods. Histone methylation is one mechanism that is known to regulate gene expression at the transcriptional level. Here, we measured relative protein levels of seven histone methyltransferases (SMYD2, SETD7, ASH2L, RBBP5, SUV39H1, EHMT2, and SET8), four methylated histone H3 residues (H3K4me1, H3K9me3, H3K27me1, and H3K36me2), the methyltransferase activity on H3K4, and methylation of p53 (p53K370me2 and p53K372me1) in the skeletal muscle and liver of the freeze-tolerant wood frog (Rana sylvatica) during the freeze-thaw cycle.