Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hyponatremia in cats produced brain edema, detectable by both magnetic resonance imaging (MRI) and increased brain water, with a compensatory decrease of brain sodium. Sodium transport was measured in synaptosomes from hyponatremic cat cerebral cortex. The sodium efflux via Na(+)-K(+)-ATPase was significantly higher (144%) than control, while sodium influx via the Na+/H+ antiporter was significantly decreased (74%). Both responses tend to decrease brain intracellular sodium and thus, brain cell osmolality. Ischemia following unilateral middle cerebral artery occlusion also resulted in brain edema. However, the efflux of sodium via both Na(+)-K(+)-ATPase and sodium channels actually decreased, both maladaptive responses. Furthermore, when ischemia was superimposed upon hyponatremia, all of the cerebral adaptive changes which had been induced by hyponatremia alone were rendered ineffective. This resulted in further elevations of brain water and sodium. Hyponatremia superimposed upon ischemia thus worsens the brain edema associated with ischemia alone. Thus, ischemia impairs the ability of the brain to adapt to hyponatremia, probably by eliminating the compensatory mechanisms of brain sodium transport initiated by hyponatremia.
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PMID:Severe brain edema associated with cumulative effects of hyponatremic encephalopathy and ischemic hypoxia. 797 57

Hypoxemia is a major comorbid factor for permanent brain damage in several metabolic encephalopathies. To determine whether hypoxia impairs brain adaptation to hyponatremia, worsening brain edema, we performed in vitro and in vivo studies in cats and rats with hyponatremia plus either ischemic or hypoxic hypoxia. Mortality with hypoxic hypoxia was 0%; with hyponatremia, 22%; and with hyponatremia+hypoxia, 100%. Hyponatremia in cats produced brain edema, with a compensatory decrease of brain sodium. Ischemic hypoxia also resulted in brain edema, but with elevation of brain sodium. However, when ischemic hypoxia was superimposed upon hyponatremia, there was elevation of brain sodium with further elevation of water. Outward sodium transport in cat cerebral cortex synaptosomes was measured via three major pathways through which brain osmolality can be decreased. After hyponatremia, sodium transport was significantly altered such that brain cell osmolality would decrease: 44% increase in Na(+)-K(+)-ATPase transport activity (ouabain inhibitable); 26% decrease in amiloride-sensitive sodium uptake. The change in veratridine-stimulated sodium uptake was not significant (P > 0.05). When ischemic hypoxia was superimposed upon hyponatremia, all of the cerebral adaptive changes induced by hyponatremia alone were eliminated. Thus, hypoxia combined with hyponatremia produces a major increase in brain edema and mortality, probably by eliminating the compensatory mechanisms of sodium transport initiated by hyponatremia that tend to minimize brain swelling.
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PMID:Hypoxic and ischemic hypoxia exacerbate brain injury associated with metabolic encephalopathy in laboratory animals. 828 95

The physicochemical properties of water enable it to act as a solvent for electrolytes, and to influence the molecular configuration and hence the function--enzymatic in particular--of polypeptide chains in biological systems. The association of water with electrolytes determines the osmotic regulation of cell volume and allows the establishment of the transmembrane ion concentration gradients that underlie nerve excitation and impulse conduction. Fluid in the central nervous system is distributed in the intracellular and extracellular spaces (ICS, ECS) of the brain parenchyma, the cerebrospinal fluid, and the vascular compartment--the brain capillaries and small arteries and veins. Regulated exchange of fluid between these various compartments occurs at the blood-brain barrier (BBB), and at the ventricular ependyma and choroid plexus, and, on the brain surface, at the pia mater. The normal BBB is relatively permeable to water, but considerably less so to ions, including the principal electrolytes Brain fluid regulation takes place within the context of systemic fluid volume control, which depends on the mutual interaction of osmo-, volume-, and pressure-receptors in the hypothalamus, heart and kidney, hormones such as vasopressin, renin-angiotensin, aldosterone, atriopeptins, and digitalis-like immunoreactive substance, and their respective sites of action. Evidence for specific transport capabilities of the cerebral capillary endothelium, for example high Na+K(+)-ATPase activity and the presence at the abluminal surface of a Na(+)--H+ antiporter, suggests that cerebral microvessels play a more active part in brain volume regulation and ion homoeostasis than do capillaries in other vascular beds. The normal brain ECS amounts to 12-19% of brain volume, and is markedly reduced in anoxia, ischaemia, metabolic poisoning, spreading depression, and conventional procedures for histological fixation. The asymmetrical distributions of Na+ K+ and Ca2+ between ICS and ECS underlie the roles of these cations in nerve excitation and conduction, and in signal transduction. The relatively large volume of the CSF, and extensive diffusional exchange of many substances between brain ECS and CSF, augment the ion-homeostasing capacity of the ECS. The choroid plexus, in addition to secreting CSF principally by biochemical mechanisms (there is an additional small component from the extracellular fluid), actively transports some substances from the blood (e.g. nucleotides and ascorbic acid), and actively removes others from the CSF. In contrast with CSF secretion, CSF reabsorption is principally a biomechanical process, passively dependent on the CSF-dural sinus pressure gradient. Pathological increases in intracranial water content imply development of an intracranial mass lesion. The additional water may be distributed diffusely within the brain parenchyma as brain oedema, as a cyst, or as increase in ventricular volume due to hydrocephalus. Brain oedema is classified on the basis of pathophysiology into four categories, vasogenic, cytotoxic, osmotic and hydrostatic. The clinical conditions in which brain oedema presents the greatest problems are tumour, ischaemia, and head injury. Peritumoural oedema is predominantly vasogenic and related to BBB dysfunction. Ischaemic oedema is initially cytotoxic, with a shift of Na+ and CI- ions from ECS to ICS, followed by osmotically obliged water, this shift can be detected by diffusion-weighted MRI. Later in the evolution of an ischaemic lesion the oedema becomes vasogenic, with disruption of the BBB. Recent imaging studies in patients with head injury suggest that the development of traumatic brain oedema may follow a biphasic time course similar to that of ischaemic oedema. Hydrocephalus is associated in the great majority of cases with an obstruction to the circulation or drainage of CSF, or, occasionally, with overproduction of CSF by a choroid plexus papilloma. In either case, the consequence is a ris
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PMID:The normal and pathological physiology of brain water. 907 71

Two major types of brain edema may be discriminated, characterized by intra- or extracellular fluid accumulation. Intracellular (cytotoxic) edema is found after cerebral ischemia, trauma, intoxications, and metabolic disorders. Pathogenetic mechanisms include (1) failure of active Na+ export via Na/K-ATPase because of energy shortage, (2) increased Na+-permeability, or (3) activation of Na+-driven membrane pumps. The latter mechanism reflects homeostatic functions of astroglia, which at reduced availability of energy resources uses the remaining Na+-gradient to fuel uptake of transmitters such as glutamate, and for control of pH(i). Extracellular (vasogenic) edema is caused by damage to the blood-brain barrier and consists of protein-rich fluid. It accompanies brain tumors, trauma, infections, and hypertensive crisis. Pathogenetic mechanisms include (1) opening of tight junctions responsible for barrier opening in acute conditions, or (2) sprouting of immature blood vessels in chronic conditions such as brain tumors.
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PMID:Cerebral edema. 1132 Apr 99

The aim of the present study was to determine the potential therapeutic value of 21-aminosteroid U-74389G, on blood-brain barrier (BBB) breakdown and edema in association with the changes in synaptosomal Na(+)/K(+) and Mg(2+)/Ca(2+)-ATPase activities in rat brain subjected to post-ischemic reperfusion injury. Brain ischemia was achieved by means of four-vessel occlusion model for 25 min and animals were sacrificed after 12 h reperfusion. An increase of cerebral tissue water content, blood-brain disruption and the changes of synaptosomal Na(+)/K(+) and Mg(2+)/Ca(2+)-ATPases activities were evaluated. U-74389G was given intraperitoneally at two times as 5 mg/kg at 10 min prior to ischemia and at the beginning of reperfusion. Edema was determined by means of wet-dried weight method, and BBB of extravasation of Evan's blue dye. Extravasation of Evan's blue dye into brain following ischemia and reperfusion was 2.4-fold of control value and brought close to control levels by the effect of U-74389G (p<0.001). Post-ischemic reperfusion injury caused an increase of 3.7% in tissue water content of whole brain and administration of U-74389G lowered the cerebral edema (p<0.001). The loses in the Na(+)/K(+)-ATPase and Mg(2+)/Ca(2+)-ATPase activities occurred as 42.1% (p<0.01) and 65.7% (p<0.001) of control value, respectively. While Mg(2+)/Ca(2+)-ATPase activity was enhanced compared to vehicle-treated group of animals (p<0.01), Na(+)/K(+)-ATPase activity was fully recovered when compared to control by U-74389G (p>0.05). U-74389G also significantly attenuated neuronal necrosis (p<0.001) which was determined in the hippocampal CA1 subfield. Blood-brain barrier protection, attenuation of brain edema and neuronal necrosis concomitant with the stabilizing of membrane-bound enzymes brought about by the effect of U-74389G suggest that 21-aminosteroids are worthy of consideration in the acute treatment of cerebral ischemia.
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PMID:Lazaroid U-74389G attenuates edema in rat brain subjected to post-ischemic reperfusion injury. 1456 34

Brain edema that forms during the early stages of stroke involves increased transport of Na+ and Cl- across an intact blood-brain barrier (BBB). Our previous studies have shown that a luminal BBB Na+-K+-Cl- cotransporter is stimulated by conditions present during ischemia and that inhibition of the cotransporter by intravenous bumetanide greatly reduces edema formation in the rat middle cerebral artery occlusion model of stroke. The present study focused on investigating the effects of hypoxia, which develops rapidly in the brain during ischemia, on the activity and expression of the BBB Na+-K+-Cl- cotransporter, as well as on Na+-K+-ATPase activity, cell ATP content, and intracellular volume. Cerebral microvascular endothelial cells (CMECs) were assessed for Na+-K+-Cl- cotransporter and Na+-K+-ATPase activities as bumetanide-sensitive and ouabain-sensitive 86Rb influxes, respectively. ATP content was assessed by luciferase assay and intracellular volume by [3H]-3-O-methyl-D-glucose and [14C]-sucrose equilibration. We found that 30-min exposure of CMECs to hypoxia ranging from 7.5% to 0.5% O2 (vs. 19% normoxic O2) significantly increased cotransporter activity as did 7.5% or 2% O2 for up to 2 h. This was not associated with reduction in Na+-K+-ATPase activity or ATP content. CMEC intracellular volume increased only after 4 to 5 h of hypoxia. Furthermore, glucose and pyruvate deprivation increased cotransporter activity under both normoxic and hypoxic conditions. Finally, we found that hypoxia increased phosphorylation but not abundance of the cotransporter protein. These findings support the hypothesis that hypoxia stimulation of the BBB Na+-K+-Cl- cotransporter contributes to ischemia-induced brain edema formation.
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PMID:Moderate-to-severe ischemic conditions increase activity and phosphorylation of the cerebral microvascular endothelial cell Na+-K+-Cl- cotransporter. 1607 89

Over the past 20 years it has become increasingly apparent that hyponatremic encephalopathy is a major cause of inhospital morbidity and mortality, particularly in postoperative patients. The factors that may lead to death or permanent brain damage and the susceptible patient groups have been gradually elucidated. Hyponatremic encephalopathy most commonly leads to brain damage in young women and in prepubescent children. The causes of brain damage include brain edema, cerebral hypoxemia, decreased brain blood flow, increased intracranial pressure, and improper therapy. Cerebral hypoxia occurs through a combination of impaired brain adaptation and cerebral vasoconstriction. Brain adaptation consists largely of brain cell loss of sodium and potassium by means of the Na-K adenosine triphosphatase (ATPase) system. There is also loss of organic osmolytes. The brain Na-K ATPase system is impaired by a combination of vasopressin plus estrogen and is stimulated by testosterone. Similarly, vasopressin plus estrogen leads to cerebral vasoconstriction, resulting in a decrement of brain oxygen utilization and cerebral blood flow. Vasopressin also directly decreases brain production of ATP. The combination leads to hypoxic brain damage, which appears to be the major cause of brain damage associated with hyponatremic encephalopathy. Measurement of arterial PO2 in patients with symptomatic hyponatremia usually demonstrates a PO2 <50 mm Hg. Improper therapy is another possible cause of brain damage in patients with hyponatremic encephalopathy. The type and distribution of such lesions are similar to those found in patients with hyponatremic encephalopathy who have severe hypoxia. Current scientific knowledge indicates that patient survival can be improved through aggressive treatment of hypoxia associated with hyponatremic encephalopathy, particularly in young women.
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PMID:Influence of hypoxia and sex on hyponatremic encephalopathy. 1684 87

This study was aimed to examine whether the changes of protein expression of sodium transporters in the ischemic penumbra are associated with the pathogenesis of ischemia-induced brain edema and/or brain cell injury. An experimental model of cerebral ischemia was made by permanent middle cerebral artery occlusion (pMCAO) in rats and the changes of protein expression of sodium transporters in the ischemic penumbra were examined by immunoblotting. Extensive infarction was observed in the frontal and parietal cortical and subcortical areas at 3 and 6h after pMCAO. Immunoblotting analyses revealed significantly increased expressions of electrogenic NBC (241 +/- 11% at 3 h and 154 +/- 9% at 6 h, P < 0.05) and NHE1 (144 +/- 3% at 3 h and 170 +/- 9% at 6 h, P < 0.05), compared with sham-operated controls. In contrast, Na-K-ATPase expression (78 +/- 6% at 3 h and 85 +/- 3% at 6 h, P < 0.05) was significantly decreased. The expression of NCX1 was unchanged at 3 h, but was significantly increased at 6 h (141 +/- 3%, P < 0.05). In addition, the expressions of neuronal (NeuN) and astroglial cell (GFAP) proteins were decreased, whereas the expression of oligodendrocyte protein (CNPase) was unchanged. Taken together, the selectively increased expressions of NHE1, electrogenic NBC, and NCX1 and decreased expression of Na-K-ATPase in the ischemic penumbra are likely to contribute to the secondary brain cell damages presumably through intracellular Na(+) accumulation, cell swelling, and intracellular Ca(2+) overload.
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PMID:Altered expression of sodium transporters in ischemic penumbra after focal cerebral ischemia in rats. 1766 98

Oxidative stress has detrimental effects in several models of neurodegenerative diseases, including subarachnoid hemorrhage (SAH). This study investigated the putative neuroprotective effect of melatonin, a powerful antioxidant, in a rat model of SAH. Male Wistar albino rats were divided as control, vehicle-treated SAH, and melatonin-treated (10 mg/kg, i.p.) SAH groups. To induce SAH, 0.3 mL blood was injected into cisterna magna of rats. Forty-eight hours after SAH induction, neurological examination scores were measured and the rats were decapitated. Brain tissue samples were taken for blood-brain barrier (BBB) permeability, brain water content, histological examination, or determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO), and Na+-K+-ATPase activities. Formation of reactive oxygen species in brain tissue samples was monitored by using a chemiluminescence (CL) technique. The neurological examination scores were increased in SAH groups on the second day of SAH induction and SAH caused a significant decrease in brain GSH content and Na+-K+-ATPase activity, which was accompanied with significant increases in CL, MDA levels, and MPO activity. On the other hand, melatonin treatment reversed all these biochemical indices as well as SAH-induced histopathological alterations, while increased brain water content and impaired BBB were also reversed by melatonin treatment. This study suggests that melatonin, which can easily cross BBB, alleviates SAH-induced oxidative stress and exerts neuroprotection by preserving BBB permeability and by reducing brain edema.
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PMID:Melatonin reduces experimental subarachnoid hemorrhage-induced oxidative brain damage and neurological symptoms. 1921 74

Traumatic brain injury (TBI) was induced by a weight-drop device using 300 g-1 m weight-height impact. The study groups were: control, alpha-lipoic acid (LA) (100 mg/kg, po), TBI, and TBI + LA (100 mg/kg, po). Forty-eight hours after the injury, neurological scores were measured and brain samples were taken for histological examination or determination of thiobarbituric acid reactive substances (TBARS) and glutathione (GSH) levels, myeloperoxidase (MPO) and Na(+)-K(+) ATPase activities, whereas cytokines (TNF-alpha, IL-1beta) were determined in blood. Brain oedema was evaluated by wet-dry weight method and blood-brain barrier (BBB) permeability was evaluated by Evans Blue (EB) extravasation. As a result, neurological scores mildly increased in trauma groups. Moreover, TBI caused a significant decrease in brain GSH and Na(+)-K(+) ATPase activity, which was accompanied with significant increases in TBARS level, MPO activity and plasma proinflammatory cytokines. LA treatment reversed all these biochemical indices as well as histopathological alterations. TBI also caused a significant increase in brain water content and EB extravasation which were partially reversed by LA treatment. These findings suggest that LA exerts neuroprotection by preserving BBB permeability and by reducing brain oedema probably by its anti-inflammatory and antioxidant properties in the TBI model.
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PMID:The protective effect of alpha lipoic acid against traumatic brain injury in rats. 1946 25


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