Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0003129 (Anoxia)
 551 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Anoxia has been compared with ischaemia. The abrupt restoration of either oxygen of flow may accelerate cardiac damage. Anoxic stimulation of glycolysis (Pasteur effect) is inhibited during ischaemia by lactate and proton accumulation at the levels of phosphofructokinase and glyceraldehyde-3-phosphate dehydrogenase. Anaerobic glycolysis provides lactate and ATP; breakdown of the latter provides protons. During partial respiration thought to occur in partial ischaemia, continued production of CO2 is a factor contributing to intracellular acidosis; mitochondrial ATP when formed by continued respiration also yields protons when ultimately broken down. The endoproducts of aerobic glycolysis (pyruvate and NADH) are transported into the mitochondria by the malate-aspartate cycle and by pyruvate dehydrogenase activity. Adenine nucleotide transferase activity normally transfers the mitochondrially-made ATP to the cytoplasm, but acyl CoA accumulates in ischaemia (or during perfusions with high circulating free fatty acids) to inhibit the transferase. The mitochondrial creatine kinase is thought to transform ATP transported outwards into creatine phosphate which can permeate the outer mitochondrial membrane. Further compartmentation of ATP may be by other creatine kinase isoenzymes or in relation to the cell membrane. The glycogenolytic-sarcoplasmic reticulum complex links a glycogen pool to the sarcoplasmic reticulum. Cyclic AMP may regulate admission of calcium to the cell during the plateau of the action potential and promote calcium uptake by the sarcoplasmic reticulum by phosphorylation of phospholamban. The latter promotes the activity of the calcium-transport ATPase. Calcium and cyclic AMP may also interact at the level of the contractile proteins where cyclic AMP phosphrylates troponin. Cyclic GMP generally has opposite effects to cyclic AMP and undergoes opposite changes in the frog cardiac cycle to those of cyclic AMP. A present it is reasonable to suppose that physiological effects of adrenaline or of cholinergic agents on the myocardium are mediated by cyclic AMP or cyclic GMP, respectively, but this hypothesis still lacks firm support. There is an association between tissue cyclic AMP and ventricular fibrillation after coronary ligation, and direct evidence for a role of cyclic AMP in promoting arrhythmias has been obtained by studies on the ventricular fibrillation threshold in the rat heart. However, there are other mechanisms, involving first the effects of substrates on the action potential duration, and secondly, the fast channel, which can also give rise to the development of malignant arrhythmias.
 ...
PMID:Myocardial metabolism and heart disease. 3 41

1. Metabolic and ionic requirements for the intra-axonal transport of dopamine beta-hydroxylase (DBH) were investigated in the cat hypogastric nerve-inferior mesenteric ganglion preparation in vitro by monitoring the enzyme accumulation above a crush, 2-2.5 cm distal to the ganglion.2. DBH accumulation in the proximal segment immediately above the crush increased linearly up to 6 h, during incubation in normal Krebs solution at 37 degrees C. The rate of transport of the enzyme was about 4 mm/h.3. Removal of the ganglion, electrical stimulation or reserpine pretreatment (1-6 days before the experiment) did not modify the rate of DBH accumulation.4. Anoxia and glucose deprivation, singly, did not affect accumulation of DBH; however, the combined treatment of anoxia plus glucose deprivation, or dinitrophenol plus glucose deprivation, very markedly interfered with accumulation.5. Removal of sodium or potassium from Krebs solution markedly inhibited the transport of DBH. Preincubation of the nerve in a high-calcium Krebs solution at 4 degrees C, and then reincubation at 37 degrees C, prevented the enzyme accumulation.6. N-ethylmaleimide, ouabain and oligomycin markedly inhibited the transport of DBH.7. The results suggest that transport of DBH, and therefore of noradrenaline storage vesicles, within the hypogastic nerve is dependent on metabolic energy derived from either glycolysis or oxidative phosphorylation. It is also suggested that the sodium-potassium-activated ATPase may play an important role in the intra-axonal transport of storage vesicles.
 ...
PMID:Metabolic and ionic requirements for the axoplasmic transport of dopamine beta-hydroxylase. 414 Feb 29

White matter of the brain and spinal cord is susceptible to anoxia and ischemia. Irreversible injury to this tissue can have serious consequences for the overall function of the CNS through disruption of signal transmission. Myelinated axons of the CNS are critically dependent on a continuous supply of energy largely generated through oxidative phosphorylation. Anoxia and ischemia cause rapid energy depletion, failure of the Na(+)-K(+)-ATPase, and accumulation of axoplasmic Na+ through noninactivating Na+ channels, with concentrations approaching 100 mmol/L after 60 minutes of anoxia. Coupled with severe K+ depletion that results in large membrane depolarization, high [Na+]i stimulates reverse Na(+)-Ca2+ exchange and axonal Ca2+ overload. A component of Ca2+ entry occurs directly through Na+ channels. The excessive accumulation of Ca2+ in turn activates various Ca(2+)-dependent enzymes, such as calpain, phospholipases, and protein kinase C, resulting in irreversible injury. The latter enzyme may be involved in "autoprotection," triggered by release of endogenous gamma-aminobutyric acid and adenosine, by modulation of certain elements responsible for deregulation of ion homeostasis. Glycolytic block, in contrast to anoxia alone, appears to preferentially mobilize internal Ca2+ stores; as control of internal Ca2+ pools is lost, excessive release from this compartment may itself contribute to axonal damage. Reoxygenation paradoxically accelerates injury in many axons, possibly as a result of severe mitochondrial Ca2+ overload leading to a secondary failure of respiration. Although glia are relatively resistant to anoxia, oligodendrocytes and the myelin sheath may be damaged by glutamate released by reverse Na(+)-glutamate transport. Use-dependent Na+ channel blockers, particularly charged compounds such as QX-314, are highly neuroprotective in vitro, but only agents that exist partially in a neutral form, such as mexiletine and tocainide, are effective after systemic administration, because charged species cannot penetrate the blood-brain barrier easily. These concepts may also apply to other white matter disorders, such as spinal cord injury or diffuse axonal injury in brain trauma. Moreover, whereas many events are unique to white matter injury, a number of steps are common to both gray and white matter anoxia and ischemia. Optimal protection of the CNS as a whole will therefore require combination therapy aimed at unique steps in gray and white matter regions, or intervention at common points in the injury cascades.
 ...
PMID:Anoxic and ischemic injury of myelinated axons in CNS white matter: from mechanistic concepts to therapeutics. 942 2

Cucumber plants (Cucumis sativus L.) with incipient Fe deficiency showed increased root capacity to reduce chelated Fe(3+) compared to Fe-sufficient plants. When Fe-ethylenediaminete-traacetate was added to the root medium of the Fe-deficient plants, the reductase activity was associated with acidification of the medium and an increase in the net apparent K(+) efflux. In the presence of the H(+)-ATPase inhibitor N,N'-dicyclohexylcarbodiimide the net apparent H(+) efflux was completely suppressed, though some reductase activity was preserved, and the net apparent K(+) efflux was significantly increased. The inhibition of the reductase activity by N,N'-dicyclohexylcarbodiimide was similar whether the pH of the medium was buffered or not. Anoxia and the protonophore carbonyl cyanide m-chlorophenyl hydrazone also caused a similar inhibition of the reductase activity. It is proposed that this redox system transports electrons only and that its activity is inhibited by plasmamembrane depolarization and anoxia. The H(+) and K(+) efflux associated with the reductase activity may be a result of the plasmamembrane depolarization it causes.
 ...
PMID:Plasmalemma redox activity and h extrusion in roots of fe-deficient cucumber plants. 1666 94

Ischemia-reperfusion (I-R) injury causes several diseases, including acute kidney injury. Hibernating mammals survive periods of torpor with a marked drop in tissue perfusion, interspersed with periods of arousal, and consequently I-R injury. In the present study, sensitivity to anoxia and/or reoxygenation and alterations in cellular ATP and homeostasis of the two most energy consuming processes, protein translation and Na+-K+-ATPase function, were evaluated in renal proximal tubular epithelial cells of mouse or native hibernator hamster origin. Compared with the mouse cells, the hamster cells were less sensitive to anoxia and reoxygenation and ATP was preserved under anoxia. Anoxia triggered mechanisms that suppress protein translation in both species. However, under anoxia, the activity of ATPase, which is mostly attributed to Na+-K+-ATPase function, remained stable in the hamster cells but decreased in the mouse cells. In normoxia, ATPase activity in hamster cells was considerably lower than that in mouse cells. As the Na+-K+-ATPase pump preserves the ion gradient against passive leakage through ion channels, the lower energy demand for the function of this pump in hamster cells may indicate less ion leakage due to fewer ion channels. In accordance with this hypothesis, ouabain-treated hamster cells had a higher survival rate than mouse cells, indicating fewer ion channels and consequently slower deregulation of intracellular ion concentration and cell death due to Na+-K+-ATPase inhibition. Therefore, it is likely that the conserved energy from the suppression of protein translation is adequate enough to support the lower energy demand for Na+-K+-ATPase function and cell survival of hamster cells under anoxia. Clarifying how cells of a native hibernator manage energy under warm I-R may reveal novel and possible clinically applicable pathways for preventing I-R injury.
 ...
PMID:Energy handling in renal tubular epithelial cells of the hamster, a native hibernator, under warm anoxia or reoxygenation. 3054 78