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PloS One 2014Paraoxonase 1 (PON1) is a protein found associated with high density lipoprotein (HDL), thought to prevent oxidative modification of low-density lipoprotein (LDL). This...
BACKGROUND
Paraoxonase 1 (PON1) is a protein found associated with high density lipoprotein (HDL), thought to prevent oxidative modification of low-density lipoprotein (LDL). This enzyme has been implicated in lowering the risk of cardiovascular disease. Anoxia-reoxygenation and oxidative stress are important elements in cardiovascular and cerebrovascular disease. However, the role of PON1 in anoxia-reoxygenation or anoxic injury is unclear. We hypothesize that PON1 prevents anoxia-reoxygenation injury. We set out to determine whether PON1 expression in Drosophila melanogaster protects against anoxia-reoxygenation (A-R) induced injury.
METHODS
Wild type (WT) and transgenic PON1 flies were exposed to anoxia (100% Nitrogen) for different time intervals (from 1 to 24 hours). After the anoxic period, flies were placed in room air for reoxygenation. Activity and survival of flies was then recorded.
RESULTS
Within 5 minutes of anoxia, all flies fell into a stupor state. After reoxygenation, survivor flies resumed activity with some delay. Interestingly, transgenic flies recovered from stupor later than WT. PON1 transgenic flies had a significant survival advantage after A-R stress compared with WT. The protection conferred by PON1 expression was present regardless of the age or dietary restriction. Furthermore, PON1 expression exclusively in CNS conferred protection.
CONCLUSION
Our results support the hypothesis that PON1 has a protective role in anoxia-reoxygenation injury, and its expression in the CNS is sufficient and necessary to provide a 100% survival protection.
Topics: Animals; Animals, Genetically Modified; Aryldialkylphosphatase; Central Nervous System; Diet; Disease Models, Animal; Drosophila melanogaster; Gene Expression; Hypoxia; Male; Oxidative Stress; Polymorphism, Genetic; Reactive Oxygen Species
PubMed: 24400090
DOI: 10.1371/journal.pone.0084434 -
Experimental Physiology Dec 2019• What is the topic of this review? To explore the unique evolutionary origins of the human brain and critically appraise its energy budget, including limits of oxygen... (Review)
Review
NEW FINDINGS
• What is the topic of this review? To explore the unique evolutionary origins of the human brain and critically appraise its energy budget, including limits of oxygen and glucose deprivation during anoxia and ischaemia. • What advances does it highlight? The brain appears to be more resilient to substrate depletion than traditionally thought, highlighting greater resilience and an underappreciated capacity for functional recovery.
ABSTRACT
The human brain has evolved into an unusually large, complex and metabolically expensive organ that relies entirely on a continuous supply of O and glucose. It has traditionally been assumed that its exorbitant energy budget, combined with little to no energy reserves, renders it especially vulnerable to anoxia and ischaemia, with substrate depletion and progression towards cell death largely irreversible and rapid. However, new and exciting evidence suggests that neurons can survive for longer than previously thought, highlighting an unexpected resilience and underappreciated capacity for functional recovery that has changed the way we think about brain cell death. Nature has the potential to unlock some of the mysteries underlying ischaemic survival, with select vertebrates having solved the problem of anoxia-hypoxia tolerance over millions of years of evolution. Better understanding of their survival strategies, including remarkable adaptations in brain physiology and redox homeostasis, might help to identify new therapeutic targets for human diseases characterized by O deprivation, ischaemia-reperfusion injury and ageing.
Topics: Adaptation, Physiological; Animals; Brain Death; Energy Metabolism; Glucose; Humans; Hypoxia; Oxygen
PubMed: 31605408
DOI: 10.1113/EP088005 -
The American Journal of Physiology Jul 1982Among the biochemical processes initiated by anoxia or ischemia that play a central role in cellular injury during deprivation is an alteration in cellular hydrogen ion...
Among the biochemical processes initiated by anoxia or ischemia that play a central role in cellular injury during deprivation is an alteration in cellular hydrogen ion concentration. In this study, the rate of exchange of intracellular hydrogen ion concentration in canine brain was compared with that in liver, using the 5,5-dimethyloxazolidine-2,4-dione method during anoxia at 37 and at 20 degrees C. The intracellular pH of brain decreased more rapidly than it did in liver anoxia at 37 degrees C. The intracellular pH of neither brain nor liver changed substantially during 30 min of anoxia at 20 degrees C. Although the ratio of tissue to plasma water did not change, the calculated extracellular-to-intracellular volume ratio increased during 30 min of anoxia at 37 but not at 20 degrees C.
Topics: Animals; Body Water; Brain; Dogs; Hydrogen-Ion Concentration; Hypothermia; Hypoxia; Hypoxia, Brain; Kinetics; Liver
PubMed: 7091362
DOI: 10.1152/ajpcell.1982.243.1.C62 -
Physiological Research 1999The cation-osmotic hemolysis was studied in human red blood cells incubated under anoxic conditions. In relation to the time course of anoxia, two phases of hemolysis...
The cation-osmotic hemolysis was studied in human red blood cells incubated under anoxic conditions. In relation to the time course of anoxia, two phases of hemolysis were distinguished. A significant decrease of hemolysis was found between 3 and 24 h of incubation. On the other hand, hemolysis was significantly increased after prolonged incubation (48-72 h). Using the method of cation-osmotic hemolysis, the properties of two membrane constituents, spectrine membrane skeleton and membrane bilayer, were studied. The relation between cation-osmotic hemolysis and erythrocyte deformability is being discussed.
Topics: Erythrocyte Membrane; Erythrocytes; Hemolysis; Humans; Hypoxia
PubMed: 10523058
DOI: No ID Found -
The American Journal of Physiology Jul 1993Chrysemys picta bellii is well known for its ability to survive extended anoxic periods and has been widely used as a model system to study anoxic metabolism. Described...
Chrysemys picta bellii is well known for its ability to survive extended anoxic periods and has been widely used as a model system to study anoxic metabolism. Described here is a method for the isolation of anoxia-tolerant hepatocytes from this species. Freshly isolated hepatocytes were determined to be viable based on trypan blue exclusion, gluconeogenic capacity from [14C]lactate, responsiveness to epinephrine and glucagon, and maintenance of cellular adenylate concentrations. Under anoxic conditions for 10 h there was no significant increase in cell staining and no decrease in cellular ATP concentration. Furthermore, the addition of cyanide at the 5-h mark did not result in any significant differences in these parameters; however, iodoacetate added at this time caused trypan blue staining to increase and ATP concentrations to fall. The rate of glucose production from the cells was threefold greater under anoxic than normoxic conditions, underscoring the important role of the liver in supplying substrate during anoxia. From the rate of O2 consumption and rate of lactate production under anaerobic conditions, ATP turnover rates were calculated to be 68.4 +/- 7.2 and 6.5 +/- 0.43 mumol ATP.g-1.h-1, respectively; this corresponds to a 90% decrease in metabolic rate during anoxia. Within a cellular system such as this the more complex regulatory mechanisms involved in a large coordinated reduction in metabolism can be probed.
Topics: Adaptation, Physiological; Animals; Carbohydrate Metabolism; Cell Separation; Female; Hypoxia; Liver; Oxygen Consumption; Turtles
PubMed: 8342699
DOI: 10.1152/ajpregu.1993.265.1.R49 -
Cardiovascular Clinics 1971
Review
Topics: Heart Diseases; Heart Failure; Hemoglobins; Humans; Hypoxia; Lung Diseases; Osmotic Pressure; Oxygen; Postoperative Complications; Pulmonary Alveoli; Pulmonary Circulation; Respiration; Respiratory Insufficiency; Smoking; Ventilators, Mechanical
PubMed: 4946018
DOI: No ID Found -
Przeglad Lekarski 1989
Review
Topics: Coronary Disease; Humans; Hypoxia; Myocardium; Oxygen Consumption; Philosophy, Medical
PubMed: 2672114
DOI: No ID Found -
International Journal of Hyperthermia :... Sep 2018Transcriptional hypoxia-inducible factor-1α (HIF-1α) plays the fundamental role in adaptive processes in response to hypoxia. Specific HIF-1α target genes are...
Transcriptional hypoxia-inducible factor-1α (HIF-1α) plays the fundamental role in adaptive processes in response to hypoxia. Specific HIF-1α target genes are involved in glycolysis, erythropoiesis and angiogenesis to promote survival. In our previous study we have demonstrated that naturally low body temperature of newborn rats protects them against damage due to perinatal hypoxia. Therefore, our experiments aimed at checking the effects of body temperature during simulated perinatal anoxia on subsequent changes of expression of HIF-1α and its specific target genes such as vascular endothelial growth factor (VEGF) and erythropoietin (EPO) in the rat brain. Two-day old Wistar rats were divided into three temperature groups: normothermic -33 °C, hyperthermic -37 °C and extremely hyperthermic -39 °C. The temperature was controlled 15 min before start and continued during 10 min of anoxia as well as for 2 h post-anoxia. HIF-1α was analysed by Western blot and immunofluorescence and mRNA levels of HIF-1α and its downstream genes (VEGF, EPO) were quantified by qRT-PCR. Thermal conditions during neonatal anoxia affected the hippocampal and neocortical level of HIF-1α protein. Physiological body temperature of newborn rats led to prominent accumulation of cerebral HIF-1α protein and significant upregulation of VEGF and EPO mRNA. In contrast, anoxia-induced HIF-1α activation at elevated body temperatures was less pronounced. Since HIF-1α and EPO have recently been regarded as promising therapeutical targets against brain lesions due to hypoxia/ischemia, presented data imply that in order to achieve a full effect of neuroprotection, the thermal conditions during and after the insult should be taken into consideration.
Topics: Animals; Brain; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Rats; Rats, Wistar; Temperature
PubMed: 28974122
DOI: 10.1080/02656736.2017.1385860 -
Progress in Neurobiology May 1996Hypoxia threatens brain function during the entire life-span starting from early fetal age up to senescence. This review compares the short-term, long-term and... (Review)
Review
Hypoxia threatens brain function during the entire life-span starting from early fetal age up to senescence. This review compares the short-term, long-term and life-spanning effects of fetal chronic hypoxia and neonatal anoxia on several behavioural paradigms including novelty-induced spontaneous and learning behaviours. Furthermore, it reveals that perinatal hypoxia is an additional threat to neurodegeneration and decline of cognitive and other behaviours during the aging process. Prenatal hypoxia evokes a temporary delay of ingrowth of cholinergic and serotonergic fibres into the hippocampus and neocortex, and causes an enhanced neurodegeneration of 5-HT-ir axons during aging. Neonatal anoxia suppresses hippocampal ChAT activity and up-regulates muscarinic receptor sites for 3H-QNB and 3H-pirenzepine binding in the hippocampus in the early postnatal age. The altered development of axonal arborization and pre- and postsynaptic cholinergic functions may be an important underlying mechanism to explain the behavioural deficits. As far as the cellular mechanisms of perinatal hypoxia is concerned, our primary aim was to study the putative importance of Ca2+ homeostasis of developing neurons by means of pharmacological interventions and by measuring the development of immunoexpression of Ca(2+)-binding proteins. We assessed that nimodipine, an L-type calcium channel blocker, prevented or attenuated the adverse behavioural and neurochemical effects of perinatal hypoxias, while it enhanced the early postnatal development of ir-Ca(2+)-binding proteins. The results are discussed in the context of different related research areas on brain development and hypoxia and ischaemia.
Topics: Animals; Behavior; Brain; Humans; Hypoxia; Neurotransmitter Agents
PubMed: 8817697
DOI: 10.1016/0301-0082(96)00007-x -
Journal of Clinical and Experimental... 1955
Topics: Convulsive Therapy; Electricity; Electroconvulsive Therapy; Hypoxia
PubMed: 13271537
DOI: No ID Found