Hypoxia tolerance in reptiles, amphibians, and fishes: life with variable oxygen availability.

The ability of fishes, amphibians, and reptiles to survive extremes of oxygen availability derives from a core triad of adaptations: profound metabolic suppression, tolerance of ionic and pH disturbances, and mechanisms for avoiding free-radical injury during reoxygenation. For long-term anoxic survival, enhanced storage of glycogen in critical tissues is also necessary. The diversity of body morphologies and habitats and the utilization of dormancy have resulted in a broad array of adaptations to hypoxia in lower vertebrates. For example, the most anoxia-tolerant vertebrates, painted turtles and crucian carp, meet the challenge of variable oxygen in fundamentally different ways: Turtles undergo near-suspended animation, whereas carp remain active and responsive in the absence of oxygen. Although the mechanisms of survival in both of these cases include large stores of glycogen and drastically decreased metabolism, other mechanisms, such as regulation of ion channels in excitable membranes, are apparently divergent. Common themes in the regulatory adjustments to hypoxia involve control of metabolism and ion channel conductance by protein phosphorylation. Tolerance of decreased energy charge and accumulating anaerobic end products as well as enhanced antioxidant defenses and regenerative capacities are also key to hypoxia survival in lower vertebrates.

[1]  J. Ramirez,et al.  Hypoxia tolerance in mammals and birds: from the wilderness to the clinic. , 2007, Annual review of physiology.

[2]  C. Wood,et al.  Tribute to R. G. Boutilier: The effect of size on the physiological and behavioural responses of oscar, Astronotus ocellatus, to hypoxia , 2006, Journal of Experimental Biology.

[3]  D. Segrè,et al.  Supporting Online Material Materials and Methods Tables S1 and S2 References the Effect of Oxygen on Biochemical Networks and the Evolution of Complex Life , 2022 .

[4]  Anoop Kumar,et al.  Appendage Regeneration in Adult Vertebrates and Implications for Regenerative Medicine , 2005, Science.

[5]  P. Falkowski,et al.  The Rise of Oxygen over the Past 205 Million Years and the Evolution of Large Placental Mammals , 2005, Science.

[6]  Damian S Shin,et al.  Calcium and protein phosphatase 1/2A attenuate N-methyl-D-aspartate receptor activity in the anoxic turtle cortex. , 2005, Comparative biochemistry and physiology. Part A, Molecular & integrative physiology.

[7]  J. Cameron,et al.  Cardioprotective effects of KATP channel activation during hypoxia in goldfish Carassius auratus , 2005, Journal of Experimental Biology.

[8]  L. C. Gomes,et al.  Metabolic adjustments in two Amazonian cichlids exposed to hypoxia and anoxia. , 2005, Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology.

[9]  J. Daut,et al.  K(ATP) channels and preconditioning: a re-examination of the role of mitochondrial K(ATP) channels and an overview of alternative mechanisms. , 2005, Journal of molecular and cellular cardiology.

[10]  J. Iverson,et al.  Survival and Physiological Responses of Hatchling Blanding’s Turtles (Emydoidea blandingii) to Submergence in Normoxic and Hypoxic Water under Simulated Winter Conditions , 2005, Physiological and Biochemical Zoology.

[11]  Jiankun Cui,et al.  Brain-Specific Knock-Out of Hypoxia-Inducible Factor-1α Reduces Rather Than Increases Hypoxic-Ischemic Damage , 2005, The Journal of Neuroscience.

[12]  R. Huey,et al.  Hypoxia, Global Warming, and Terrestrial Late Permian Extinctions , 2005, Science.

[13]  J. P. Costanzo,et al.  Anoxia tolerance and freeze tolerance in hatchling turtles , 2005, Journal of Comparative Physiology B.

[14]  P. Bickler,et al.  Intracellular calcium and survival of tadpole forebrain cells in anoxia , 2005, Journal of Experimental Biology.

[15]  D. Jackson Surviving extreme lactic acidosis: the role of calcium lactate formation in the anoxic turtle , 2004, Respiratory Physiology & Neurobiology.

[16]  J. Lindsley,et al.  Nutrient sensing and metabolic decisions. , 2004, Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology.

[17]  L. Buck Adenosine as a signal for ion channel arrest in anoxia-tolerant organisms. , 2004, Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology.

[18]  M. Guppy The biochemistry of metabolic depression: a history of perceptions. , 2004, Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology.

[19]  L. Buck,et al.  Time-dependent expression of heat shock proteins 70 and 90 in tissues of the anoxic western painted turtle , 2004, Journal of Experimental Biology.

[20]  A. Farrell,et al.  Maintained Cardiac Pumping in Anoxic Crucian Carp , 2004, Science.

[21]  G. Nilsson,et al.  Hypoxic survival strategies in two fishes: extreme anoxia tolerance in the North European crucian carp and natural hypoxic preconditioning in a coral-reef shark , 2004, Journal of Experimental Biology.

[22]  D. Jackson Acid–base balance during hypoxic hypometabolism: selected vertebrate strategies , 2004, Respiratory Physiology & Neurobiology.

[23]  P. Lutz,et al.  Vertebrate brains at the pilot light , 2004, Respiratory Physiology & Neurobiology.

[24]  K. Rodnick,et al.  All rainbow trout (Oncorhynchus mykiss) are not created equal: intra-specific variation in cardiac hypoxia tolerance , 2004, Journal of Experimental Biology.

[25]  G. Grover,et al.  The mitochondrial KATP channel opener BMS-191095 induces neuronal preconditioning , 2004, Neuroreport.

[26]  G. Nilsson,et al.  Hypoxia in paradise: widespread hypoxia tolerance in coral reef fishes , 2004, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[27]  G. R. Ultsch,et al.  The Physiology of Hibernation in Canadian Leopard Frogs (Rana pipiens) and Bullfrogs (Rana catesbeiana) , 2004, Physiological and Biochemical Zoology.

[28]  J. Cameron,et al.  A role for nitric oxide in hypoxia-induced activation of cardiac KATP channels in goldfish (Carassius auratus) , 2003, Journal of Experimental Biology.

[29]  P. Lutz,et al.  Slow death in the leopard frog Rana pipiens: neurotransmitters and anoxia tolerance , 2003, Journal of Experimental Biology.

[30]  T. Weissman,et al.  Neurogenic radial glial cells in reptile, rodent and human: from mitosis to migration. , 2003, Cerebral cortex.

[31]  Michael V. Cohen,et al.  Mitochondrial KATP channels in preconditioning , 2003 .

[32]  M. Brand,et al.  Tissue-specific depression of mitochondrial proton leak and substrate oxidation in hibernating arctic ground squirrels. , 2003, American journal of physiology. Regulatory, integrative and comparative physiology.

[33]  G. R. Ultsch,et al.  Hibernation in freshwater turtles: softshell turtles (Apalone spinifera) are the most intolerant of anoxia among North American species , 2003, Journal of Comparative Physiology B.

[34]  Damian S Shin,et al.  Effect of Anoxia and Pharmacological Anoxia on Whole‐Cell NMDA Receptor Currents in Cortical Neurons from the Western Painted Turtle , 2003, Physiological and Biochemical Zoology.

[35]  J. Rast,et al.  Identification of low-abundance differentially expressed transcripts using arrayed cDNA clones. , 2002, Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology.

[36]  Marcelo Hermes-Lima,et al.  Animal response to drastic changes in oxygen availability and physiological oxidative stress. , 2002, Comparative biochemistry and physiology. Toxicology & pharmacology : CBP.

[37]  M. Brand,et al.  Topology of Superoxide Production from Different Sites in the Mitochondrial Electron Transport Chain* , 2002, The Journal of Biological Chemistry.

[38]  K. Storey,et al.  Life in the slow lane: molecular mechanisms of estivation. , 2002, Comparative biochemistry and physiology. Part A, Molecular & integrative physiology.

[39]  D. Jackson Hibernating without Oxygen: Physiological Adaptations of the Painted Turtle , 2002, The Journal of physiology.

[40]  G. R. Ultsch,et al.  The Physiology of Overwintering in a Turtle That Occupies Multiple Habitats, the Common Snapping Turtle (Chelydra serpentina) , 2002, Physiological and Biochemical Zoology.

[41]  D. Busija,et al.  MitoKATP opener, diazoxide, reduces neuronal damage after middle cerebral artery occlusion in the rat , 2002 .

[42]  R. Boutilier,et al.  Adaptive plasticity of skeletal muscle energetics in hibernating frogs: mitochondrial proton leak during metabolic depression. , 2002, The Journal of experimental biology.

[43]  L. Buck,et al.  Molecular Adaptations for Survival during Anoxia: Lessons from Lower Vertebrates , 2002, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[44]  M. Brand,et al.  Proton leak in hepatocytes and liver mitochondria from archosaurs (crocodiles) and allometric relationships for ectotherms , 2002, Journal of Comparative Physiology B.

[45]  J. García-Verdugo,et al.  Neurogenesis and Neuronal Regeneration in the Adult Reptilian Brain , 2002, Brain, Behavior and Evolution.

[46]  J. García-Verdugo,et al.  The proliferative ventricular zone in adult vertebrates: a comparative study using reptiles, birds, and mammals , 2002, Brain Research Bulletin.

[47]  Gary Fiskum,et al.  Generation of reactive oxygen species by the mitochondrial electron transport chain , 2002, Journal of neurochemistry.

[48]  M. Brand,et al.  Primary causes of decreased mitochondrial oxygen consumption during metabolic depression in snail cells. , 2002, American journal of physiology. Regulatory, integrative and comparative physiology.

[49]  A. Farrell,et al.  Recovery of trout myocardial function following anoxia: preconditioning in a non-mammalian model. , 2001, American journal of physiology. Regulatory, integrative and comparative physiology.

[50]  R. Bolli Cardioprotective function of inducible nitric oxide synthase and role of nitric oxide in myocardial ischemia and preconditioning: an overview of a decade of research. , 2001, Journal of molecular and cellular cardiology.

[51]  P. Lutz,et al.  Slow ATP loss and the defense of ion homeostasis in the anoxic frog brain. , 2001, The Journal of experimental biology.

[52]  G. Nilsson,et al.  Surviving anoxia with the brain turned on. , 2001, News in physiological sciences : an international journal of physiology produced jointly by the International Union of Physiological Sciences and the American Physiological Society.

[53]  P. Lutz,et al.  Effect of anoxia and adenosine on cerebral blood flow in the leopard frog (Rana pipiens) , 2001, Neuroscience Letters.

[54]  R. Boutilier,et al.  Mechanisms of cell survival in hypoxia and hypothermia. , 2001, The Journal of experimental biology.

[55]  M B Roth,et al.  Oxygen deprivation causes suspended animation in the zebrafish embryo , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[56]  M. Gassmann,et al.  Characterization of a hypoxia-inducible factor (HIF-1alpha ) from rainbow trout. Accumulation of protein occurs at normal venous oxygen tension. , 2001, The Journal of biological chemistry.

[57]  J. Downey,et al.  Opening of Mitochondrial KATP Channels Triggers the Preconditioned State by Generating Free Radicals , 2000, Circulation research.

[58]  C. Biasi,et al.  Action of adenosine on energetics, protein synthesis and K(+) homeostasis in teleost hepatocytes. , 2000, The Journal of experimental biology.

[59]  D. Jackson How a Turtle's Shell Helps It Survive Prolonged Anoxic Acidosis. , 2000, News in physiological sciences : an international journal of physiology produced jointly by the International Union of Physiological Sciences and the American Physiological Society.

[60]  V. M. Almeida-Val,et al.  Specialized metabolism and biochemical suppression during aestivation of the extant South American lungfish--Lepidosiren paradoxa. , 2000, Brazilian journal of biology = Revista brasleira de biologia.

[61]  P. Donohoe,et al.  Hypoxia-Induced Silencing of NMDA Receptors in Turtle Neurons , 2000, The Journal of Neuroscience.

[62]  G. R. Ultsch,et al.  Lactic Acid Buffering by Bone and Shell in Anoxic Softshell and Painted Turtles , 2000, Physiological and Biochemical Zoology.

[63]  C. Biasi,et al.  Oxygen-dependent energetics of anoxia-tolerant and anoxia-intolerant hepatocytes. , 2000, The Journal of experimental biology.

[64]  D. Jackson,et al.  Living without oxygen: lessons from the freshwater turtle. , 2000, Comparative biochemistry and physiology. Part A, Molecular & integrative physiology.

[65]  F. C. Souza,et al.  Scaling effects on hypoxia tolerance in the Amazon fish Astronotus ocellatus (Perciformes: Cichlidae): contribution of tissue enzyme levels. , 2000, Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology.

[66]  P. Donohoe,et al.  Factors affecting membrane permeability and ionic homeostasis in the cold-submerged frog. , 2000, The Journal of experimental biology.

[67]  V. M. Almeida-Val,et al.  Anoxic cardiac performance in Amazonian and north-temperate-zone teleosts , 1999 .

[68]  R. Berner,et al.  Atmospheric oxygen over Phanerozoic time. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[69]  L. Buck,et al.  Acute reduction in whole cell conductance in anoxic turtle brain. , 1999, American journal of physiology. Regulatory, integrative and comparative physiology.

[70]  G. Zupanc,et al.  Neurogenesis, cell death and regeneration in the adult gymnotiform brain. , 1999, The Journal of experimental biology.

[71]  G. Nilsson,et al.  Brain blood flow and blood pressure during hypoxia in the epaulette shark Hemiscyllium ocellatum, a hypoxia-tolerant elasmobranch. , 1999, The Journal of experimental biology.

[72]  P. Withers,et al.  Metabolic depression in animals: physiological perspectives and biochemical generalizations , 1999, Biological reviews of the Cambridge Philosophical Society.

[73]  A. Terzic,et al.  Mitochondrial ATP-sensitive K+ channels modulate cardiac mitochondrial function. , 1998, American journal of physiology. Heart and circulatory physiology.

[74]  T. Vanden Hoek,et al.  Reactive Oxygen Species Released from Mitochondria during Brief Hypoxia Induce Preconditioning in Cardiomyocytes* , 1998, The Journal of Biological Chemistry.

[75]  B. Siesjö,et al.  Calcium in ischemic cell death. , 1998, Stroke.

[76]  M. Nie,et al.  Oxygen uptake in bullfrog tadpoles (Rana catesbeiana). , 1998, The Journal of experimental zoology.

[77]  L. Buck,et al.  Adenosine and anoxia reduce N-methyl-D-aspartate receptor open probability in turtle cerebrocortex. , 1998, The Journal of experimental biology.

[78]  P. Lutz,et al.  Release of adenosine and ATP in the brain of the freshwater turtle (Trachemys scripta) during long-term anoxia , 1997, Brain Research.

[79]  K. Mikoshiba,et al.  Phosphorylation-dependent Regulation ofN-Methyl-d-aspartate Receptors by Calmodulin* , 1997, The Journal of Biological Chemistry.

[80]  J. García-Verdugo,et al.  Postnatal neurogenesis in the telencephalon of turtles: evidence for nonradial migration of new neurons from distant proliferative ventricular zones to the olfactory bulbs. , 1997, Brain research. Developmental brain research.

[81]  P. W. Hochachka,et al.  Unifying theory of hypoxia tolerance: molecular/metabolic defense and rescue mechanisms for surviving oxygen lack. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[82]  R. Huganir,et al.  Inactivation of NMDA Receptors by Direct Interaction of Calmodulin with the NR1 Subunit , 1996, Cell.

[83]  L. Buck,et al.  Role of adenosine in NMDA receptor modulation in the cerebral cortex of an anoxia-tolerant turtle (Chrysemys picta belli). , 1995, The Journal of experimental biology.

[84]  M. Rice,et al.  High Levels of Ascorbic Acid, Not Glutathione, in the CNS of Anoxia‐Tolerant Reptiles Contrasted with Levels in Anoxia‐Intolerant Species , 1995, Journal of neurochemistry.

[85]  P. Lutz,et al.  Time Course of Anoxia-Induced Increase in Cerebral Blood Flow Rate in Turtles: Evidence for a Role of Adenosine , 1994, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[86]  G. Nilsson,et al.  Anoxia and adenosine induce increased cerebral blood flow rate in crucian carp. , 1994, The American journal of physiology.

[87]  P. Lutz,et al.  The Brain Without Oxygen: Causes of Failure-Physiological and Molecular Mechanisms for Survival , 1994 .

[88]  P. W. Hochachka,et al.  Anoxic suppression of Na(+)-K(+)-ATPase and constant membrane potential in hepatocytes: support for channel arrest. , 1993, The American journal of physiology.

[89]  S. Hourani,et al.  Adenosine receptor subtypes. , 1993, Trends in pharmacological sciences.

[90]  K. Storey,et al.  Antioxidant defenses in the tolerance of freezing and anoxia by garter snakes. , 1993, The American journal of physiology.

[91]  P. Lutz,et al.  Journal of Cerebral Blood Flow and Metabolism Adenosine, a "retaliatory" Metabolite, Promotes Anoxia Tolerance in Turtle Brain , 2022 .

[92]  Christian Rosenmund,et al.  Calcium-induced actin depolymerization reduces NMDA channel activity , 1993, Neuron.

[93]  A. Polenov,et al.  Ultrastructural radioautographic analysis of neurogenesis in the hypothalamus of the adult frog, Rana temporaria, with special reference to physiological regeneration of the preoptic nucleus , 1993, Cell and Tissue Research.

[94]  D. Mash,et al.  Downregulation of sodium channels during anoxia: a putative survival strategy of turtle brain. , 1992, The American journal of physiology.

[95]  G. Nilsson,et al.  The adenosine receptor blocker aminophylline increases anoxic ethanol excretion in crucian carp. , 1991, The American journal of physiology.

[96]  T. Higuti,et al.  ATP-sensitive K+ channel in the mitochondrial inner membrane , 1991, Nature.

[97]  Richard W. Brill,et al.  Cardiorespiratory responses of skipjack tuna (Katsuwonus pelamis), yellowfin tuna (Thunnus albacares), and bigeye tuna (Thunnus obesus) to acute reductions of ambient oxygen , 1990 .

[98]  A. Farrell,et al.  Effects of Hypoxia and Drugs on the Cardiovascular Dynamics of the Atlantic Hagfish Myxine Glutinosa , 1990 .

[99]  M. Nakazawa,et al.  Adenosine: A Retaliatory Metabolite or Not? , 1990 .

[100]  J. Nemcsók,et al.  The effects of hypoxia and paraquat on the superoxide dismutase activity in different organs of carp, Cyprinus carpio L. , 1989 .

[101]  J. García-Verdugo,et al.  Delayed postnatal neurogenesis in the cerebral cortex of lizards. , 1988, Brain research.

[102]  D. Jackson,et al.  Brain and cerebrospinal fluid ion composition after long-term anoxia in diving turtles. , 1988, The American journal of physiology.

[103]  A. Hulbert,et al.  Evolution of mammalian endothermic metabolism: "leaky" membranes as a source of heat. , 1987, The American journal of physiology.

[104]  P. W. Hochachka Defense strategies against hypoxia and hypothermia. , 1986, Science.

[105]  G. R. Ultsch,et al.  The Comparative Physiology of Diving in North American Freshwater Turtles. II. Plasma Ion Balance during Prolonged Anoxia , 1984, Physiological Zoology.

[106]  D. Bradford Winterkill, Oxygen Relations, and Energy Metabolism of a Submerged Dormant Amphibian, Rana Muscosa , 1983 .

[107]  S. Easter,et al.  Postembryonic growth of the optic tectum in goldfish. I. Location of germinal cells and numbers of neurons produced , 1983, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[108]  J. LaManna,et al.  Brain potassium ion homeostasis, anoxia, and metabolic inhibition in turtles and rats. , 1982, The American journal of physiology.

[109]  R. Coggeshall,et al.  Neuronal increase in various areas of the nervous system of the guppy, Lebistes , 1980, The Journal of comparative neurology.

[110]  E. Shoubridge,et al.  Ethanol: novel end product of vertebrate anaerobic metabolism. , 1980, Science.

[111]  H. Gesser The effects of hypoxia and reoxygenation on force development in myocardia of carp and rainbow trout: protective effects of CO2/HCO3. , 1977, The Journal of experimental biology.

[112]  R. Vannucci,et al.  CARBOHYDRATE AND ENERGY METABOLISM IN PERINATAL RAT BRAIN: RELATION TO SURVIVAL IN ANOXIA , 1975, Journal of neurochemistry.

[113]  R. Seymour,et al.  Gas transport and blood acid-base balance in diving sea snakes. , 1975, The Journal of experimental zoology.

[114]  D. Penney,et al.  Anaerobic glycolysis and lactic acid accumulation in cold submergedRana pipiens , 1973, Journal of comparative physiology.

[115]  P. Gorer,et al.  THE PHYSIOLOGY OF HIBERNATION , 1930 .

[116]  V. Lushchak,et al.  Oxidative stress and antioxidant defenses in goldfish Carassius auratus during anoxia and reoxygenation. , 2001, American journal of physiology. Regulatory, integrative and comparative physiology.

[117]  G. Semenza,et al.  Regulation of mammalian O2 homeostasis by hypoxia-inducible factor 1. , 1999, Annual review of cell and developmental biology.

[118]  K. Storey Survival under stress: molecular mechanisms of metabolic rate depression in animals , 1998 .

[119]  P. Lutz,et al.  Contrasting strategies for anoxic brain survival--glycolysis up or down. , 1997, The Journal of experimental biology.

[120]  K. Storey,et al.  Metabolic adaptations supporting anoxia tolerance in reptiles: recent advances. , 1996, Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology.

[121]  P. Lutz,et al.  Short Communication: Adenosine Release in the Anoxic Turtle Brain: A Possible Mechanism for Anoxic Survival , 1992 .

[122]  S. Filoni,et al.  Transient expression of glial-fibrillary acidic protein (GFAP) in the ependyma of the regenerating spinal cord in adult newts. , 1991, Journal fur Hirnforschung.

[123]  G. R. Ultsch The viability of nearctic freshwater turtles submerged in anoxia and normoxia at 3 and 10°C , 1985 .

[124]  R. S. Lillo Heart rate and blood pressure in bullfrogs during prolonged maintenance in water at low temperature , 1980 .

[125]  A. Polenov,et al.  The role of the ependyma of the recessus praeopticus in formation and the physiological regeneration of the nucleus praeopticus in lower vertebrates. , 1972, Zeitschrift fur mikroskopisch-anatomische Forschung.