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Relative oxidation of glutamate and glucose by vertebrate erythrocytes.

1. Lungfish erythrocytes (RBC), unlike those in other species of fishes, oxidize endogenous glutamate at a higher rate than they oxidize glucose. This pattern closely resembles that found in invertebrates. 2. The exogenous glutamate oxidation rate of RBC from most species of fish as well as other groups of vertebrates is approximately equal to or less than that observed for glucose. 3. These findings suggest that the nucleated RBC of most vertebrates appear to rely less on the TCA cycle for energy production and more on the glycolytic metabolism of carbohydrates. 4. The RBC of lungfish are also distinguished from RBC of other vertebrates by their relatively higher permeability to exogenous substrates. For example, chicken RBC have a glucose accumulation rate which is approximately one third that observed for lungfish RBC at twice the medium glucose concentration. 5. The unique characteristics of lungfish RBC may be related to their adaptation to the high concentrations of urea produced during estivation.

Animals↗

Vasotocin and hydrin 2 (vasotocinyl-Gly) in the African toad Bufo regularis: study under various environmental conditions.

1. The neurohypophysial osmoregulatory hormones of the African toad Bufo regularis, a species adapted to estivate under dry and hot conditions, have been investigated. Vasotocin and hydrin 2 (vasotocinyl-Gly) have been identified by their retention times in high-pressure reverse-phase liquid chromatography and coelution with synthetic peptides, their pharmacological properties (vasotocin) and microsequencing. 2. Vasotocin-associated neurophysin (MSEL-neurophysin type) has been characterized by its N-terminal amino acid sequence. 3. In toads subjected to dehydration by evaporation (20% weight loss) or to osmotic stress by immersion in 2% NaCl for 3 hr (6% weight loss), the molar ratio hydrin 2/vasotocin (about 2:1) remained similar to the one observed in control animals. 4. In toads exposed to saline solution, there was a large decrease (roughly 30%) in the amounts of both hormones in the neuro-hypophysis. Environmental conditions for distinct secretions of vasotocin and hydrin 2 remain to be found.

Amino Acid Sequence↗

Metabolic adaptations supporting anoxia tolerance in reptiles: recent advances.

Animal survival during severe hypoxia and/or anoxia is enhanced by a variety of biochemical adaptations including adaptations of fermentative pathways of energy production and, most importantly, the ability to sharply reduce metabolic rate by 5-20 fold and enter a hypometabolic state. The biochemical regulation of metabolic arrest is proving to have common molecular principles that extend across phylogenetic lines and that are conserved in different types of arrested states (not only anaerobiosis but also estivation, hibernation, etc.). Our new studies with anoxia-tolerant vertebrates have identified a variety of regulatory mechanisms involved in both metabolic rate depression and in the aerobic recovery process using as models the freshwater turtle Trachemys scripta elegans and garter snakes Thamnophis sirtalis parietalis. Mechanisms include: 1) post-translational modification of cellular and functional proteins by reversible phosphorylation and changes in protein kinase (PKA, PKC) and/or phosphatase activities to regulate this, 2) reversible enzyme binding associations with subcellular structural elements, 3) differential gene expression and/or mRNA translation producing new mRNA variants and new protein products, 4) changes in protease activity, particularly the multicatalytic proteinase complex, and 5) both constitutive and anoxia-induced modifications to cellular antioxidant systems to deal with oxidative stress during the anoxic-aerobic transition of recovery.

Adaptation, Physiological↗

Adventures in oxygen metabolism.

Peter W. Hochachka led a grand life of science adventure and left as his legacy a whole new field--biochemical adaptation. Oxygen was at the core of Peter's career and his laboratory made major contributions to our understanding of how animals deal with variation in oxygen availability in many forms. He analyzed the molecular mechanisms that support facultative anaerobiosis, studied muscle exercise metabolism for high speed flight, swimming and running, investigated mammalian diving on many trips to the Antarctic to study Weddell seals, and probed the metabolic and genetic adaptations that provide optimal hypoxia tolerance for humans residing at high altitudes. His work illuminated both biochemical and physiological mechanisms that are used to optimize aerobic metabolism, to compensate for hypoxic insults, and to conserve energy by strong metabolic rate depression under anoxia. His articles, books and lectures galvanized the field with leading-edge insights and theories and he consistently challenged comparative biochemists to use their unique model systems to explore the range and breadth of animal strategies of biochemical adaptation. Lessons drawn from my training in Peter's laboratory have led me on continuing explorations of adaptations in enzyme function, signal transduction, gene expression, and antioxidant defenses ranging over systems of anoxia tolerance, freezing survival, estivation, and mammalian hibernation.

Adaptation, Physiological↗

Metabolic depression in hibernation and major depression: an explanatory theory and an animal model of depression.

Metabolic depression, an adaptive biological process for energy preservation, is responsible for torpor, hibernation and estivation. We propose that a form of metabolic depression, and not mitochondrial dysfunction, is the process underlying the observed hypometabolism, state-dependent neurobiological changes and vegetative symptoms of major depression in humans. The process of metabolic depression is reactivated via differential gene expression in response to perceived adverse stimuli in predisposed persons. Behavior inhibition by temperament, anxiety disorders, genetic vulnerabilities, and early traumatic experiences predispose persons to depression. The proposed theory is supported by similarities in the presentation and neurobiology of hibernation in bears and major depression and explains the yet unexplained neurobiological changes of depression. Although, gene expression is suppressed in other hibernators by deep hypothermia, bears were chosen because they hibernate with mild hypothermia. Pre-hibernation in bears and major depression with atypical features are both characterized by fat storage through overeating, oversleeping, and decreased mobility. Hibernation in bears and major depression with melancholic features are characterized by withdrawal from the environment, lack of energy, loss of weight from not eating and burning stored fat, changes in sleep pattern, and the following similar neurobiological findings: reversible subclinical hypothyroidism; increased concentration of serum cortisol; acute phase protein response; low respiratory quotient; oxidative stress response; decreased neurotransmitter levels; and changes in cyclic-adenosine monophosphate-binding activity. Signaling systems associated with protein phosphorylation, transcription factors, and gene expression are responsible for the metabolic depression process during pre-hibernation and hibernation. Antidepressants and mood stabilizers interfere with the hibernation process and produce their therapeutic effects by normalizing the fluctuation of activities in the different signaling systems, which are down-regulated during hibernation and depression and up-regulated during exodus from hibernation and the hypomanic or manic phase of mood disorders. The ways individuals cognitively perceive, understand, communicate, and react to the vegetative symptoms of depression, from downregulation in energy production, and in the absence of known medical causes, produce the other characteristics of depression including guilt, helplessness, hopelessness, suicidal phenomena, agitation, panic attacks, psychotic symptoms, and sudden switch to hypomanic or manic episodes. The presence of one or more of these characteristics depends on the person's neuropsychological function, its social status between the others, and the other's response to the person. Neurobiological changes associated with metabolic depression during entrance, maintenance, and exodus from hibernation in bears is suggested as a natural animal model of human depression and mood disorders.

Animals↗

Vasopressin and galanin expression in the hypothalamus of two African rodents, Taterillus gracilis and Steatomys caurinus, subjected to water-restriction.

The expression of arginine-vasopressin (AVP) and galanin (GAL) was studied by immunohistochemistry and in situ hybridization in the hypothalamus of two species of African rodents. In the wild, these animals experience successive arid and wet seasons that alternately stimulate their antidiuretic and diuretic systems. In this study, animals were subjected to both standardized laboratory conditions and to eight days of water-restriction. Under both sets of conditions, AVP and GAL were detected in the supraoptic nucleus (SON), paraventricular nucleus (PVN), and median eminence (ME). AVP and GAL responses to water-restriction differed in the two species, as did behavioral adaptations to the hot-dry season. In Taterillus gracilis, AVP- and GAL-LI (like immunoreactivity) peptide and mRNA levels increased in the SON. AVP-LI peptide and mRNA levels increased in the PVN, whereas only AVP-LI peptide levels increased in the ME. Pituitary gland AVP pools were unchanged by water deprivation, whereas urinary AVP levels and osmolality increased. The AVP response is typical of that of desert rodents, favoring survival under conditions of water-restriction. In Steatomys caurinus, which estivates, AVP and GAL-LI peptide levels decreased in the hypothalamus, as they did in the laboratory rat. In the SON, AVP, and GAL mRNA levels increased, whereas, in the PVN, only AVP mRNA levels increased. Pituitary gland AVP levels decreased, whereas urinary AVP levels and osmolality increased. In both species, the changes in the amount of GAL-LI peptide appeared to be closely linked to changes in AVP levels, suggesting that this peptide is involved in the osmoregulatory response to water-restriction.

Africa↗

[Photosensitivity in human pathology: mechanisms and clinical aspects].

Photosensitivity diseases are reviewed. The pathogenesis of photodermatoses is not completely elucidated, especially because the photosensitizing agents are rarely identified. In exogenous photosensitization, the chemical agent (chromophore) is most often identified, reaching the skin either via topical contact or by systemic administration (drugs). Concepts of phototoxicity (photochemical reaction) and photo-allergy (photo-immunologic reaction) explain the clinical aspects. Dermatoses with photosensitivity are divided into three groups: photo-aggravated dermatoses (solar herpes, lupus erythematosus), photosensitivity caused by protective system defect (xeroderma pigmentosum), and photosensitivity caused by metabolic defects (porphyrias, pellagra). Idiopathic photodermatoses (unknown chromophore) are triggered by solar exposure (systemic photo-allergens would serve as mediators): 'benign estival polymorphous light eruption', polymorphous light eruptions, persistent light reactor, solar urticaria.

Adult↗

Urea and amphibian water economy.

Accumulation of urea in the body fluids enables some amphibians to tolerate high ambient salinities (Bufo viridis, Xenopus laevis, Rana cancrivora, Ambystoma tigrinum, Batrachoseps spp.) or to estivate in soil with low water potentials (Scaphiopus spp.). These species are assumed not only to accumulate urea produced in the normal metabolism, but to synthesize urea in response to water shortage. Re-examination of the data did not support the view of an osmoregulatory urea synthesis. Increased urea synthesis on exposure to high salinities in X. laevis, R. cancrivora and Batrachoseps spp. seemed to reflect reactions to an adverse environment. It is suggested that in amphibians, solute concentration in the plasma and rate of excretion of urea are coordinated so that at a certain plasma concentration, urea is excreted at the same rate at which it is produced. The higher the level of urea in the body fluids at balance between production and excretion, the higher the tolerance of the species of low external water potentials. The mechanisms that integrate the relationship between plasma solute concentration and handling of urea by the kidneys are not known.

Adaptation, Physiological↗

Regulation of body water balance in reedfrogs (superspecies Hyperolius viridiflavus and Hyperolius marmoratus: Amphibia, Anura, Hyperoliidae) living in unpredictably varying savannah environments.

The regulation of body water balance was examined in the reedfrogs Hyperolius marmoratus taeniatus and Hyperolius viridiflavus ommatostictus. Temperature and stage of post-metamorphic development significantly affected the rate of water uptake. Hydrated reedfrogs prevented hyperhydration by voiding diluted urine when obtaining water. Within 48 hr after rehydration, body fluid osmolality remained at low levels, which may be supportive to counter excessive cutaneous water influx in hydrated frogs. Once evaporative water loss exceeded 10-12% total body mass, reedfrogs became anuric. The rate of water uptake strongly increased with increasing body water deficit. Both the anuric response and the increased rate of water uptake are assumed to strongly enhance the efficacy of using very briefly available water sources during dry-period conditions. Dry-adapted and estivating reedfrogs survived evaporative water losses between 40 and 55% total body mass. Bladder fluid stores contributed substantially to this desiccation tolerance. During a 16-day period of desiccation, H. v. ommatostictus could replace approximately 25% of evaporative water loss from the bladder fluid store. During desiccation, the level of free amino acids selectively increased in the gastrocnemius muscle tissue, which may support cell volume regulation and/or protect cellular structures from osmotic stresses. Even strongly dehydrated reedfrogs rehydrated quickly with no obvious osmoregulatory problem. Rehydration was associated with a higher than expected decrease of free amino acids in the gastrocnemius muscle tissue, a response that may help to protect cells from bursting during fast rehydration.

Amino Acids↗

Comparison between the antioxidant status of terrestrial and diving mammals.

Many diving mammals are known for their ability to deal with nitrogen supersaturation and to tolerate apnea for extended periods. They are all characterized by high oxygen-carrying capacity in blood together with high oxygen storage in their muscle mass due to large myoglobin concentrations. The above properties theoretically also imply a high tissue antioxidant defenses (AD) to counteract reactive oxygen species (ROS) generation associated with the rapid transition from apnea to reoxygenation. Different enzymatic (superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase, and glutathione S-transferase), and non-enzymatic (levels of glutathione) AD as well as cellular damage (thiobarbituric acid-reactive substances contents, as a measure of lipoperoxidation) were measured in blood samples obtained from anesthetized animals, and also in blood obtained from recently dead diving mammals, and compared to some terrestrial mammals (n=5 in both groups). The results confirmed that diving mammals have, in general, higher antioxidant status compared to non-diving mammals. Apparently, to avoid exposure of tissues to changing high oxygen levels, and therefore to avoid an oxidative stress condition related to antioxidant consumption and increased ROS generation, diving mammals possess constitutive high levels of antioxidants in tissues. These data are in agreement with short-term AD adaptations related to torpor and to animals that experience large daily changes in oxygen consumption. These data are similar to the long-term adaptations of animals that undergo hibernation, estivation, freezing-thawing and dehydration-rehydration processes. In summary, animals that routinely face high changes in oxygen availability and/or consumption seem to show a general strategy to prevent oxidative damage by having either appropriate high constitutive AD and/or the ability to undergo arrested states, where depressed metabolic rates minimize the oxidative challenge.

Animals↗

Comparative biology and pathology of oxidative stress in Alzheimer and other neurodegenerative diseases: beyond damage and response.

In this review, we consider comparative aspects of the biology and pathology of oxygen radicals in neurodegenerative disease and how these findings have influenced our concept of oxidative stress. The common definition of oxidative stress is a breach of antioxidant defenses by oxygen radicals leading to damage to critical molecules and disrupted physiology. Inherent in this definition is that oxidative stress is an unstable situation, for if there is net damage, viability of the system decreases with time, leading to disequilibria and death. While this circumstance defines acute conditions, such as stroke and head trauma which result in dysfunction and death, it does not fit physiological situations or chronic diseases closely aligned to normal physiology. Therefore, we propose that oxidative modifications in Alzheimer disease may actually serve as a homeostatic response to stress resulting in a shift of neuronal priority from normal function to basic survival. This phenomenon is comparable to normal physiological conditions of metabolic decrease, such as those seen in hibernation and estivation. Thus, Alzheimer disease could be seen as part of normal aging that includes additional pathology due to inadequate homeostatic response.

Alzheimer Disease↗

The fine structure of the cornea of the salamanderfish, Lepidogalaxias salamandroides (Lepidogalaxiidae, Teleostei).

The salamanderfish, Lepidogalaxias salamandroides, is a small freshwater fish that is endemic to southwestern Australia. Its phylogeny is still uncertain, but it belongs to a monotypic family that is as primitive as any living teleost. Able to survive during periods of drought by burrowing into the substrate and estivating for many months, this species has evolved a unique visual system, which is highly adapted to its changing environment. Thought to use cutaneous respiration during periods of dormancy, it secretes a mucus sheath over the eyes and genital openings to inhibit desiccation. The cornea is split into dermal and scleral components, separated by an iridescent layer and a mucoid layer. The dermal cornea comprises an epithelium containing both goblet cells and mucus-secreting granules in the central region, which overlies a thick stroma of collagen lamellae. The dermal stroma possesses numerous sutural fibers and flattened keratocytes and collections of three types of pigment granulates in the periphery. Posterior to the dermal stroma lies an iridescent layer consisting of five flattened cell processes interspersed with membranous extensions of smooth endoplasmic reticula. The mucoid layer is composed of numerous membrane-bound structures that allow movement of the scleral cornea beneath the dermal cornea or secondary spectacle. The scleral stroma is thin (six to seven lamellae) contains keratocytes, and overlies a relatively thin and irregular Desçemet's membrane and a monolayered endothelium. In the iridocorneal angle and situated between Desçemet's membrane and the endothelium is an "annular ligament," which is composed of flattened cells with lobulated nuclei and a fine granular cytoplasm with a few mitochondria. The numerous corneal inclusions are discussed with respect to their phylogeny and function.

Animals↗

Lungfish Neoceratodus forsteri: activities of ornithine-urea cycle and enzymes.

The level of activity of the ornithine-urea cycle is low in the liver of the permanently aquatic Australian lungfish. The rate of incorporation of (14)C-bicarbonate into urea by liver slices was only 100th of that previously observed in the estivating African lungfish Protopterus dolloi. The activities of enzymes of the ornithine-urea cycle were similarly reduced. The low activity of this cycle in Neoceratodus is consistent with its exclusively aquatic nature.

Animals↗

Evolution of urea synthesis in vertebrates: the piscine connection.

Elasmobranch fishes, the coelacanth, estivating lungfish, amphibians, and mammals synthesize urea by the ornithine-urea cycle; by comparison, urea synthetic activity is generally insignificant in teleostean fishes. It is reported here that isolated liver cells of two teleost toadfishes, Opsanus beta and Opsansus tau, synthesize urea by the ornithine-urea cycle at substantial rates. Because toadfish excrete ammonia, do not use urea as an osmolyte, and have substantial levels of urease in their digestive systems, urea may serve as a transient nitrogen store, forming the basis of a nitrogen conservation shuttle system between liver and gut as in ruminants and hibernators. Toadfish synthesize urea using enzymes and subcellular distributions similar to those of elasmobranchs: glutamine-dependent carbamoyl phosphate synthethase (CPS III) and mitochondrial arginase. In contrast, mammals have CPS I (ammonia-dependent) and cytosolic arginase. Data on CPS and arginases in other fishes, including lungfishes and the coelacanth, support the hypothesis that the ornithine-urea cycle, a monophyletic trait in the vertebrates, underwent two key changes before the evolution of the extant lungfishes: a switch from CPS III to CPS I and replacement of mitochondrial arginase by a cytosolic equivalent.

Animals↗

The effects of hypercapnia on force and rate of contraction and intracellular pH of perfused ventricles from the land snail Helix lucorum (L.).

The effects of hypercapnia, together with low and high levels of extracellular Ca(2+), on heart activity and intracellular pH were examined in isolated perfused hearts from the land snail Helix lucorum. In addition, the intracellular level of Ca(2+) was determined in slices of ventricles superfused with both normal and hypercapnic salines, containing low and high concentrations of Ca(2+), to investigate whether low extracellular pH affects the entry of Ca(2+) into the heart cells. We also examined the effect of a saline that simulated the composition of the haemolymph of snails after estivating for 3 months on the heart activity and intracellular pH. The results showed that hypercapnia causes decreases in the rate and force of heart contraction, and these are more pronounced in the presence of low levels of extracellular Ca(2+). Moreover, the present results indicate that Ca(2+) maintains the contractility of the heart muscle under acidic conditions and seems to act by competing with protons for the Ca(2+ )binding sites on sarcolemma. The negative effect of hypercapnia on heart activity appears to be due to a reduction in extracellular pH rather than to changes in intracellular pH.

Journal Article↗

[Histoenzymologic study of the adrenal gland of the dormouse during the annual cycle].

The histoenzymologic study of the adrenals in Glis glis was realized for 4 enzymatic activities (acid phosphatase, glucose 1 phosphate dehydrogenase, delta5 3beta-hydroxysteroid dehydrogenase and cholinesterase) completed by the simultaneous dosage of glucose-6-phosphate dehydrogenase. The histophotometric measures made it possible to differentiate the enzymatic activities of the different zones of the adrenal cortex and to show the persistance of an important activity of the zona fasciculata and sometimes of the zona reticulata during hibernation, independantly of the zona glomerulosa. This study confirms the activation of the adrenal cortex during hibernation with a brutal depletion at awakening and reduced activity during estivation.

Acid Phosphatase↗

[Diversity of malaria in the Sahelo-Saharan region. A review apropos of the status in Niger, West Africa].

The concept of epidemiologic facies of malaria underlines the diversity in the expression of the disease in areas where important ecological variations interfere largely with transmission. Niger is quite a border region between the afrotropical fauna from the south and the Palearctic fauna from the north. The last one filters through the mountains where it maybe represents a relic of ancient paleoclimates. Annual variations of the northern limit of Anopheles arabiensis, in the Sahelo-Saharan region including some oasis, are related to temporary breeding places produced by seasonal rainfall, after estivation during the dry season or after a long migration with the wind. An. gambiae s.s is present in the south and along the Niger river, with An. funestus, even till Zinder. The northern limit of An. nili is the Niger river. The permanent variations of the environment induce great differences in the level of transmission between an intermediate stable situation in the south to an unstable one in the north. Epidemic outbreaks appear some years in vulnerable populations. The implementation of a malaria program supposes to take account of the various eco-epidemiologic situations all over the country. Even if mortality and morbidity became lower, natural precaution in some groups of people must be preserved.

Adolescent↗

[Photoprotection by drugs].

Medicinal photoprotection is indicated in photosensitive skin diseases and photodermatoses. Vitamin PP and para-aminobenzoic acid can be tried in benign estival polymorphous light eruptions. Carotinoids are efficient in erythropoietic protoporphyria and useful in idiopathic polymorphous light eruptions and in remanent photosensitization. Immunodepressants may be used against remanent photosensitization.

Antimalarials↗