scholarly journals GABA metabolism is crucial for long-term survival of anoxia in annual killifish embryos

2020 ◽  
Vol 223 (20) ◽  
pp. jeb229716 ◽  
Author(s):  
Daniel E. Zajic ◽  
Jason E. Podrabsky
Keyword(s):  
Metabolic Response ◽  
Anoxia Tolerance ◽  
Term Survival ◽  
Ephemeral Ponds ◽  
Annual Killifish ◽  
Gaba Metabolism ◽  
Gaba Production ◽  
Semialdehyde Dehydrogenase ◽  
Anti Oxidant ◽  
Austrofundulus Limnaeus

ABSTRACTIn most vertebrates, a lack of oxygen quickly leads to irreparable damages to vital organs, such as the brain and heart. However, there are some vertebrates that have evolved mechanisms to survive periods of no oxygen (anoxia). The annual killifish (Austrofundulus limnaeus) survives in ephemeral ponds in the coastal deserts of Venezuela and their embryos have the remarkable ability to tolerate anoxia for months. When exposed to anoxia, embryos of A. limnaeus respond by producing significant amounts of γ-aminobutyric acid (GABA). This study aims to understand the role of GABA in supporting the metabolic response to anoxia. To explore this, we investigated four developmentally distinct stages of A. limnaeus embryos that vary in their anoxia tolerance. We measured GABA and lactate concentrations across development in response to anoxia and aerobic recovery. We then inhibited enzymes responsible for the production and degradation of GABA and observed GABA and lactate concentrations, as well as embryo mortality. Here, we show for the first time that GABA metabolism affects anoxia tolerance in A. limnaeus embryos. Inhibition of enzymes responsible for GABA production (glutamate decarboxylase) and degradation (GABA-transaminase and succinic acid semialdehyde dehydrogenase) led to increased mortality, supporting a role for GABA as an intermediate product and not a metabolic end-product. We propose multiple roles for GABA during anoxia and aerobic recovery in A. limnaeus embryos, serving as a neurotransmitter, an energy source, and an anti-oxidant.

scholarly journals MitosRNAs and extreme anoxia tolerance in embryos of the annual killifish Austrofundulus limnaeus

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Claire L. Riggs ◽  
Steven Cody Woll ◽  
Jason E. Podrabsky
Keyword(s):  
Gene Expression ◽  
Mitochondrial Genome ◽  
Comparative Study ◽  
Expression Patterns ◽  
Anoxia Tolerance ◽  
Isolated Cells ◽  
Ephemeral Ponds ◽  
Annual Killifish ◽  
Small Ncrnas ◽  
Austrofundulus Limnaeus

AbstractEmbryos of the annual killifish Austrofundulus limnaeus are the most anoxia-tolerant vertebrate. Annual killifish inhabit ephemeral ponds, producing drought and anoxia-tolerant embryos, which allows the species to persist generation after generation. Anoxia tolerance and physiology vary by developmental stage, creating a unique opportunity for comparative study within the species. A recent study of small ncRNA expression in A. limnaeus embryos in response to anoxia and aerobic recovery revealed small ncRNAs with expression patterns that suggest a role in supporting anoxia tolerance. MitosRNAs, small ncRNAs derived from the mitochondrial genome, emerged as an interesting group of these sequences. MitosRNAs derived from mitochondrial tRNAs were differentially expressed in developing embryos and isolated cells exhibiting extreme anoxia tolerance. In this study we focus on expression of mitosRNAs derived from tRNA-cysteine, and their subcellular and organismal localization in order to consider possible function. These tRNA-cys mitosRNAs appear enriched in the mitochondria, particularly near the nucleus, and also appear to be present in the cytoplasm. We provide evidence that mitosRNAs are generated in the mitochondria in response to anoxia, though the precise mechanism of biosynthesis remains unclear. MitosRNAs derived from tRNA-cys localize to numerous tissues, and increase in the anterior brain during anoxia. We hypothesize that these RNAs may play a role in regulating gene expression that supports extreme anoxia tolerance.

scholarly journals Extreme anoxia tolerance in embryos of the annual killifish Austrofundulus limnaeus: insights from a metabolomics analysis

2007 ◽  
Vol 210 (13) ◽  
pp. 2253-2266 ◽  
Author(s):  
J. E. Podrabsky ◽  
J. P. Lopez ◽  
T. W. M. Fan ◽  
R. Higashi ◽  
G. N. Somero
Keyword(s):  
Anoxia Tolerance ◽  
Annual Killifish ◽  
Austrofundulus Limnaeus ◽  
Metabolomics Analysis

scholarly journals Metabolomics analysis of annual killifish (Austrofundulus limnaeus) embryos during aerial dehydration stress

2020 ◽  
Vol 52 (9) ◽  
pp. 408-422
Author(s):  
Daniel E. Zajic ◽  
Jason E. Podrabsky
Keyword(s):  
Molecular Mechanisms ◽  
Dry Season ◽  
Dehydration Stress ◽  
Aerial Exposure ◽  
Ephemeral Ponds ◽  
Annual Killifish ◽  
Metabolite Profiles ◽  
Aquatic Vertebrates ◽  
Austrofundulus Limnaeus ◽  
Insight Into

The annual killifish, Austrofundulus limnaeus, survives in ephemeral ponds in the coastal deserts of Venezuela. Persistence through the dry season is dependent on drought-resistant eggs embedded in the pond sediments during the rainy season. The ability of these embryos to enter drastic metabolic dormancy (diapause) during normal development enables A. limnaeus to survive conditions lethal to most other aquatic vertebrates; critical to the survival of the species is the ability of embryos to survive months and perhaps years without access to liquid water. Little is known about the molecular mechanisms that aid in survival of the dry season. This study aims to gain insight into the mechanisms facilitating survival of dehydration stress due to aerial exposure by examining metabolite profiles of dormant and developing embryos. There is strong evidence for unique metabolic profiles based on developmental stage and length of aerial exposure. Actively developing embryos exhibit more robust changes; however, dormant embryos respond in an active manner and significantly alter their metabolic profile. A number of metabolites accumulate in aerial-exposed embryos that may play an important role in survival, including the identification of known antioxidants and neuroprotectants. In addition, a number of unique metabolites not yet discussed in the dehydration literature are identified, such as lanthionine and 2-hydroxyglutarate. Despite high oxygen availability, embryos accumulate the anaerobic end product lactate. This paper offers an overview of the metabolic changes occurring that may support embryonic survival during dehydration stress due to aerial incubation, which can be functionally tested using genetic and pharmacological approaches.

scholarly journals Small noncoding RNA expression during extreme anoxia tolerance of annual killifish (Austrofundulus limnaeus) embryos

2017 ◽  
Vol 49 (9) ◽  
pp. 505-518 ◽  
Author(s):  
Claire L. Riggs ◽  
Jason E. Podrabsky
Keyword(s):  
Noncoding Rna ◽  
Expression Profiles ◽  
Global Analysis ◽  
Differentially Expressed ◽  
Anoxia Tolerance ◽  
Small Noncoding Rna ◽  
Death Studies ◽  
Small Noncoding Rnas ◽  
Annual Killifish ◽  
Austrofundulus Limnaeus

Small noncoding RNAs (sncRNA) have recently emerged as specific and rapid regulators of gene expression, involved in a myriad of cellular and organismal processes. MicroRNAs, a class of sncRNAs, are differentially expressed in diverse taxa in response to environmental stress, including anoxia. In most vertebrates, a brief period of oxygen deprivation results in severe tissue damage or death. Studies on sncRNA and anoxia have focused on these anoxia-sensitive species. Studying sncRNAs in anoxia-tolerant organisms may provide insight into adaptive mechanisms supporting anoxia tolerance. Embryos of the annual killifish Austrofundulus limnaeus are the most anoxia-tolerant vertebrates known, surviving over 100 days at their peak tolerance at 25°C. Their anoxia tolerance and physiology vary over development, such that both anoxia-tolerant and anoxia-sensitive phenotypes comprise the species. This allows for a robust comparison to identify sncRNAs essential to anoxia-tolerance. For this study, RNA sequencing was used to identify and quantify expression of sncRNAs in four embryonic stages of A. limnaeus in response to an exposure to anoxia and subsequent aerobic recovery. Unique stage-specific patterns of expression were identified that correlate with anoxia tolerance. In addition, embryos of A. limnaeus appear to constitutively express stress-responsive miRNAs. Most differentially expressed sncRNAs were expressed at higher levels during recovery. Many novel groups of sncRNAs with expression profiles suggesting a key role in anoxia tolerance were identified, including sncRNAs derived from mitochondrial tRNAs. This global analysis has revealed groups of candidate sncRNAs that we hypothesize support anoxia tolerance.

The bioenergetics of embryonic diapause in an annual killifish, austrofundulus limnaeus

1999 ◽  
Vol 202 (19) ◽  
pp. 2567-2580 ◽  
Author(s):  
J.E. Podrabsky ◽  
S.C. Hand
Keyword(s):  
Oxygen Consumption ◽  
Early Development ◽  
Energy Use ◽  
Heat Dissipation ◽  
Energy Charge ◽  
Adenylate Energy Charge ◽  
Ephemeral Ponds ◽  
Annual Killifish ◽  
Rate Of Oxygen Consumption ◽  
Austrofundulus Limnaeus

The annual killifish Austrofundulus limnaeus inhabits ephemeral ponds that dry out on a seasonal basis, thereby killing the adult and juvenile forms. Populations persist because diapausing embryos become embedded in the pond sediments. The rate of oxygen consumption of diapause II embryos is depressed by up to 90 % compared with that of developing embryos, and a parallel reduction is observed in heart rate. Developmental arrest was identified by cessation of somite proliferation and blockage of the ontogenetic increase in DNA content. Surprisingly, the arrest of metabolism and development is temporally offset as embryos reach diapause II; metabolic rate begins to decline 12 days prior to arrest of development. Release of embryos from diapause II is facilitated by increasing the light phase of the photoperiod. The rate of oxygen consumption of diapause III embryos is 84 % lower than the value preceding diapause III. The total energy flow of diapause II embryos apparently includes a contribution from anaerobic processes on the basis of calorimetric/respirometric ratios that are above the oxycaloric equivalent. Accumulations of lactate and ethanol at the expense of glycogen reserves are small or undetectable and do not account for the excess heat signal. Diapause II embryos maintain high [ATP]/[ADP] ratios and adenylate energy charge during diapause, consistent with a simultaneous depression of energy use and demand. Levels of AMP increase during early development and diapause II despite the highly charged adenylate pool. High values for [AMP]/[ATP] ratios in diapause II embryos are correlated with decreased rates of oxygen consumption and heat dissipation, which suggests a role for AMP in the depression of metabolism during early development and diapause II.

Hyperosmotic NaCl and severe hemorrhagic shock: role of the innervated lung

1981 ◽  
Vol 241 (6) ◽  
pp. H883-H890 ◽  
Author(s):  
O. U. Lopes ◽  
V. Pontieri ◽  
M. Rocha e Silva ◽  
I. T. Velasco
Keyword(s):  
Cardiac Output ◽  
Arterial Pressure ◽  
Metabolic Response ◽  
Term Survival ◽  
Long Term Survival ◽  
Vagal Blockade ◽  
Intravenous Infusions ◽  
Acid Base Equilibrium

Infusions of hyperosmotic NaCl (2,400 mosmol/l; 4 ml/kg) were given to dogs in severe hemorrhagic hypotension by intravenous injection (72 expts) or intra-aortic injection (25 expts). In 46 experiments intravenous infusions were given during bilateral blockage of the cervical vagal trunks (local anesthesia or cooling). Intravenous infusions (without vagal blockade) restore arterial pressure, cardiac output, and acid-base equilibrium to normal and cause mesenteric flow to overshoot prehemorrhage levels by 50%. These effects are stable, and indefinite survival was observed in every case. Intra-aortic infusions of hyperosmotic NaCl produce only a transient recovery of arterial pressure and cardiac output but no long-term survival. Intravenous infusions with vagal blockage produce only a transient recovery of cardiac output, with non long-term survival. Measurement of pulmonary artery blood osmolarity during and after the infusions shows that a different pattern is observed in each of these three groups and strongly indicates that the first passage of hyperosmotic blood through the pulmonary circulation at a time when vagal conduction is unimpaired is essential for the production of the full hemodynamic-metabolic response, which is needed for indefinite survival.

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