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)

We used postembedding electron microscopic immunocytochemistry with colloidal gold to determine the ultrastructural distribution of Na+,K(+)-ATPase in the sciatic and optic nerves of the rat. Using a polyclonal antiserum raised against the denatured catalytic subunit of brain Na+,K(+)-ATPase, we found immunoreactivity along the internodal axolemma of myelinated fibers in both nerves. This antiserum did not produce labeling of nodal axolemma. These results suggest that an important site of energy-dependent sodium-potassium exchange is along the internodal axolemma of myelinated fibers in the mammalian CNS and PNS and that there may be differences between the internodal and nodal forms of the enzyme.
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PMID:Immunocytochemical demonstration of Na+,K(+)-ATPase in internodal axolemma of myelinated fibers of rat sciatic and optic nerves. 164 59

Rat brain synaptosomal Na(+)-K(+)-ATPase was activated by Panax notoginseng (PNS, 0.1-1.0 mg.ml-1), fraction Rb1 (25-200 micrograms.ml-1), and fraction Rg1 (50-200 micrograms.ml-1). Activating rates were respectively 84-227%, 12-48%, and 12-22%. Results implied that Rb1 and Rg1 were not the major components of PNS, which were responsible for the activating effects. Ca(2+)-Mg(2+)-ATPase was inhibited by PNS (0.1-1.0 mg.ml-1) and Rb1 (100-200 micrograms.ml-1), but not by Rg1. It was proposed that PNS activated Na(+)-K(+)-ATPase, leading to a reduced Na+/Ca2+ exchange, a lowered intracellular Ca2+ level, and heart contractility.
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PMID:Effects of saponins of Panax notoginseng on sodium-potassium-adenosine triphosphatase and calcium-magnesium-adenosine triphosphatase. 166 65

There is no published description of the distribution of free Ca2+, nor of the distribution of Ca(2+)-ATPase activity associated with the maintenance of low axoplasmic Ca2+ concentrations, in normal central myelinated nerve fibres. We have used the oxalate-pyroantimonate technique to localise free Ca2+, together with the lead-citrate technique to localise Ca(2+)-ATPase activity within myelinated fibres from the adult guinea-pig optic nerve. Pyroantimonate precipitate occurred within the axoplasm at nodes of Ranvier and the internode, at areas of myelin disruption, within Schmidt-Lanterman incisures (SLI) and glial paranodal loops. But precipitate was absent from the axoplasm beneath SLI and at the paranode. Ca(2+)-ATPase activity was localised in axonal smooth endoplasmic reticulum (SER), the outer membrane of mitochondria, the nodal axolemma, the glial membranes of the paranodal loops, the SLI and the external aspect of the myelin sheath. We have demonstrated large domains within the axons of CNS fibres where calcium is present or absent. Moreover, we have shown that, where calcium is absent, there is localisation of Ca(2+)-ATPase activity, which would serve to remove calcium from the adjacent axoplasm. Our results are compared with information obtained from PNS fibres and some differences of distribution discussed.
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PMID:Localisation of calcium ions and calcium-ATPase activity within myelinated nerve fibres of the adult guinea-pig optic nerve. 183 65

A unifying metabolic hypothesis completely accounting for the development of one or more of the chronic complications of diabetes on the basis of a single aspect of disturbed glucose metabolism resulting from insulin deficiency and/or hyperglycemia has been sought by clinical and basic scientists for decades. A growing body of loosely related but internally consistent scientific data obtained from cultured cells, incubated tissue preparations, animal models, and man implicate sorbitol- and glucose-induced myo-inositol depletion and altered phosphoinositide metabolism in a series of secondary biochemical, functional, and architectural abnormalities in the PNS in diabetes. These early metabolically based functional and structural changes simulate those that characterize human diabetic neuropathy. Can abnormal phosphoinositide metabolism in diabetic nerve thereby by itself explain the development of chronic diabetic neuropathy with all of its clinical complexity and heterogeneity? Almost certainly not. Even if the entire contribution of hyperglycemia to the development of diabetic neuropathy were mediated by secondary abnormalities in phosphoinositide metabolism, other factors must also play a role. Witness the differences in the histopathological picture of neuropathy in patients with IDDM and NIDDM despite similar durations and severity of diabetes, the apparent influence of age and gender on the appearance of early neuropathy in patients with IDDM, and the association of alcohol consumption with diabetic neuropathy. While early metabolic and functional disturbances in diabetic nerve such as impaired (Na,K)-ATPase function and paranodal swelling are empirically attributable to abnormal myo-inositol and phosphoinositide metabolism, more advanced abnormalities such as axo-glial dysjunction may reflect superimposed independent biochemical and/or hormonal defects (although, as mentioned previously, aldose reductase inhibition decreases axo-glial dysjunction in diabetic humans). The PNS has only a limited repertoire of responses to a variety of insults, so that Wallerian degeneration, axonal atrophy, impaired axonal transport, and dystrophic changes in diabetic neuropathy may represent multiple factors. On the other hand, the increasingly recognized importance of the phosphoinositide cascade in neuromodulation may attribute a progressively wider range of disturbances in the diabetic PNS to myo-inositol depletion and associated defects in phosphoinositide metabolism. Thus, while all effects of aldose reductase inhibitors in the PNS of diabetic rats have been reproduced by myo-inositol supplementation when this alternative intervention has been tested, the exact role of phosphoinositide metabolism in most of these responses is not well understood.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Pathogenesis of diabetic neuropathy: role of altered phosphoinositide metabolism. 256 4

Electron probe x-ray microanalysis (EPMA) was used to measure water content (percent water) and dry weight elemental concentrations (in millimoles per kilogram) of Na, K, Cl, and Ca in axoplasm and mitochondria of rat optic and tibial nerve myelinated axons. Myelin and cytoplasm of glial cells were also analyzed. Each anatomical compartment exhibited characteristic water contents and distributions of dry weight elements, which were used to calculate respective ionized concentrations. Free axoplasmic [K+] ranged from approximately 155 mM in large PNS and CNS axons to approximately 120-130 mM in smaller fibers. Free [Na+] was approximately 15-17 mM in larger fibers compared with 20-25 mM in smaller axons, whereas free [Cl-] was found to be 30-55 mM in all axons. Because intracellular Ca is largely bound, ionized concentrations were not estimated. However, calculations of total (free plus bound) aqueous concentrations of this element showed that axoplasm of large CNS and PNS axons contained approximately 0.7 mM Ca, whereas small fibers contained 0.1-0.2 mM. Calculated ionic equilibrium potentials were as follows (in mV): in large CNS and PNS axons, E(K) = -105, E(Na) = 60, and E(Cl) = -28; in Schwann cells, E(K) = -107, E(Na) = 33, and E(Cl) = -33; and in CNS glia, E(K) = -99, E(Na) = 36, and E(Cl) = -44. Calculated resting membrane potentials were as follows (in mV, including the contribution of the Na+,K+-ATPase): large axons, about -80; small axons, about -72 to -78; and CNS glia, -91. E(Cl) is more positive than resting membrane potential in PNS and CNS axons and glia, indicating active accumulation. Direct EPMA measurement of elemental concentrations and subsequent calculation of ionized fractions in axons and glia offer fundamental neurophysiological information that has been previously unattainable.
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PMID:Intracellular concentrations of major ions in rat myelinated axons and glia: calculations based on electron probe X-ray microanalyses. 910 18

In the C57BL/Wld(s) (Wld) mouse strain, both PNS and CNS axonal disintegration during Wallerian degeneration is dramatically slowed, with isolated axons being able to conduct compound action potentials (CAPs) for several weeks post-transection. The ability to conduct a CAP signifies the presence of an intact plasma membrane, normal ion gradients, and functioning ion channels. In neurons, ion homeostasis is primarily regulated by the Na(+)-K(+)-ATPase, which utilizes approximately 50% of neuronal energy output. To investigate the possibility that the Wld mutation prolongs axonal degeneration by conferring a more favorable energetic status to neurons or alters metabolism, we used 31P and 1H magnetic resonance spectroscopy (MRS) to compare the cerebral and muscle energy metabolism, membrane phospholipid contents, and water-soluble metabolites of Wld and wild-type (C57BL/6J [6J], and BALB/c) mouse strains. We first demonstrate that, with advancing age, transected Wld CNS nerves degenerate faster, paralleling previous findings in the PNS. We found significantly decreased phosphocreatine and phosphomonoester concentrations in the brains of Wld mice at 1- and 2-months of age compared to both 6J and BALB/c mice, but we failed to find differences in the adenylate (ATP, ADP, or AMP) or phospholipid concentrations. In another excitable tissue, skeletal muscle, no differences in energy-containing metabolites were detected. High resolution 1H MRS indicated that at 1 month of age, Wld brains have cytosolic levels of glutamate and phosphocholine that are significantly decreased, relative to total N-acetyl aspartate content. Our results demonstrate that delayed Wallerian degeneration in the C57BL/Wld mouse strain is associated with altered cerebral metabolism, although these changes may be secondary to the mutation.
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PMID:Altered brain metabolism in the C57BL/Wld mouse strain detected by magnetic resonance spectroscopy: association with delayed Wallerian degeneration? 1050 Feb 67

Acrylamide (ACR) is considered to be prototypical among chemicals that cause a central-peripheral distal axonopathy. Multifocal neurofilamentous swellings and eventual degeneration of distal axon regions in the CNS and PNS have been traditionally considered the hallmark morphological features of this axonopathy. However, ACR has also been shown to produce early nerve terminal degeneration of somatosensory, somatomotor and autonomic nerve fibers under a variety of dosing conditions. Recent research from our laboratory has demonstrated that terminal degeneration precedes axonopathy during low-dose subchronic induction of neurotoxicity and occurs in the absence of axonopathy during higher-dose subacute intoxication. This relationship suggests that nerve terminal degeneration, and not axonopathy, is the primary or most important pathophysiologic lesion produced by ACR. In this hypothesis paper, we review evidence suggesting that nerve terminal degeneration is the hallmark lesion of ACR neurotoxicity, and we propose that this effect is mediated by the direct actions of ACR at nerve terminal sites. ACR is an electrophile and, therefore, sulfhydryl groups on presynaptic proteins represent rational molecular targets. Several presynaptic thiol-containing proteins (e.g. SNAP-25, NSF) are critically involved in formation of SNARE (soluble N-ethylmaleimide (NEM)-sensitive fusion protein receptor) complexes that mediate membrane fusion processes such as exocytosis and turnover of plasmalemmal proteins and other constituents. We hypothesize that ACR adduction of SNARE proteins disrupts assembly of fusion core complexes and thereby interferes with neurotransmission and presynaptic membrane turnover. General retardation of membrane turnover and accumulation of unincorporated materials could result in nerve terminal swelling and degeneration. A similar mechanism involving the long-term consequences of defective SNARE-based turnover of Na+/K(+)-ATPase and other axolemmal constituents might explain subchronic induction of axon degeneration. The ACR literature occupies a prominent position in neurotoxicology and has significantly influenced development of mechanistic hypotheses and classification schemes for neurotoxicants. Our proposal suggests a reevaluation of current classification schemes and mechanistic hypotheses that regard ACR axonopathy as a primary lesion.
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PMID:Nerve terminals as the primary site of acrylamide action: a hypothesis. 1216 47