Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The isolated choroid plexus of the rabbit takes up 5-methyltetrahydrofolate from the incubation medium. 2. Other folate analogues (pteroylglutamic acid, methotrexate, 5-formyltetrahydrofolate = folinic acid) inhibited the uptake of 5-methyltetrahydrofolate. 3. The uptake of 5-methyltetrahydrofolate was inhibited by low temperature, anaerobic conditions and dinitrophenol. 4. The anticonvulsant drugs, diphenylhydantoin and phenobarbital, had no effect on 5-methyltetrahydrofolate uptake. 5. The inhibitory effect of pteroylglutamic acid on the uptake of 5-methyltetrahydrofolate by the choroid plexus may explain the effect of long-term folic acid therapy in aggravating vitamin B12 neuropathy in pernicious anaemia.
Clin Sci Mol Med 1977 Jul
PMID:Effect of anticonvulsants on the uptake of 5-methyltetrahydrofolic acid by the choroid plexus in rabbits. 87 22

2',3'-Cyclic nucleotide 3'-phosphodiesterase (CNPase) is an enzyme associated with central nervous system myelination. Although present in the mammalian peripheral nerve, it is not clear what its role is during myelination nor how the expression of this gene is regulated in the PNS. In this study, CNPase gene expression was studied in the crushed and permanently transected rat sciatic nerve, two models of peripheral nerve neuropathy. The Schwann cells of the crushed nerve initially demyelinate, remain in a non-myelinating condition until active regeneration induces remyelination (10-21 days after injury), whereas those of the permanently transected nerve remain in a quiescent, non-myelinating state after the initial demyelination. An increase of CNPase mRNA levels is observed during degeneration and remains high whether the peripheral nerve is regenerating or not, suggesting transcriptional activation of CNPase mRNA and/or increased CNPase mRNA stability as a response to nerve injury. In contrast, the steady state level of CNPase protein did not increase during degeneration or regeneration suggesting either negative translational regulation of CNPase gene expression or a higher turnover of this protein in the injured peripheral nerve. Furthermore, CNPase activity dropped sharply during early degeneration and remained low in the quiescent cells of the permanently transected nerve while it increased in the regenerating nerve. The results suggest that although transcriptional or post-transcriptional regulation of CNPase gene expression is not dependent on Schwann cell-axonal contact, the activity of CNPase appears to be dependent on myelination and indirectly dependent on the presence of axons in the peripheral nerve.
Brain Res Mol Brain Res 1992 Sep
PMID:Regulation of 2',3'-cyclic nucleotide phosphodiesterase gene expression in experimental peripheral neuropathies. 127 49

Chronic exposure of rats to ethylene oxide (EO) causes distal axonal neuropathy of lumbosacral primary sensory neurons. To study the pathogenesis of this neuropathy, we measured rapid axonal transport in peripheral nerves. Rats were exposed for 6 h to 500 ppm EO in a chamber three times a wk for 15 wk. Rapid axonal transport and quantitative histological alterations of peripheral nerves were studied. After [35S]methionine injection into the dorsal root ganglion, the velocity of rapid anterograde axonal transport of radioisotope-labeled protein was measured. The velocity in the rats exposed to EO was 33% less than that in control rats exposed to filtered room air. However, histological differences were slight. Morphometric studies showed that in EO-exposed rats, only the distal portions of the sural nerve had significantly greater incidental degeneration of myelinated fibers than did controls. There were significantly fewer large myelinated fibers only in the distals peroneal nerve. Therefore, a decrease in the velocity of anterograde axonal transport, related to these slight histological abnormalities of the peripheral nerve, may play a causative role in the development of the distal axonal neuropathy owing to chronic EO exposure.
Mol Chem Neuropathol 1992 Dec
PMID:Rapid axonal transport velocity is reduced in experimental ethylene oxide neuropathy. 128 12

The neurological toxicity seen in patients treated with cisplatin in most cases concerns ototoxicity and peripheral neuropathy. Thus far, the pathogenesis of cisplatin neuropathy remains obscure. Yet the fact that cisplatin affects mainly the sensory peripheral nerve fibers points towards an involvement of the dorsal root ganglia. In a rat model of cisplatin neuropathy, following a cumulative dose of approx. 12 mg/kg cisplatin the sensory nerve conduction velocity began to slow as compared to age-matched controls. Peptides derived from ACTH and MSH are known to exert neurotrophic effects. In vivo they facilitate postlesion repair mechanisms in the peripheral nervous system by enhancing the early sprouting response of the damaged nerve. Surprisingly, chronic treatment with a synthetic ACTH4-9 analog not only prevented cisplatin neurotoxicity following a low or high dose regimen, but also counteracted already existing cisplatin-induced neurotoxicity. Stimulated by these findings a randomized, double blind, placebo-controlled study was performed to assess the efficacy of the peptide in the prevention of cisplatin neuropathy in women suffering from ovarian cancer. The threshold of vibration perception (VPT) was used as the principal measure of neurotoxicity. Following 6 cycles of chemotherapy the VPT had increased more than 8-fold in women receiving placebo as co-medication. Whereas the VPT in women receiving 1 mg/m2 body surface ACTH4-9 analog before and after each cisplatin cycle only increased less than 2-fold. No side effects of the peptide treatment were observed and the clinical response to the chemotherapy was similar in all treatment groups. Collectively these preclinical and clinical data suggest that treatment based on non-endocrine fragments of ACTH/MSH may be a therapeutic option in the treatment of cisplatin neuropathy.
J Steroid Biochem Mol Biol 1992 Sep
PMID:ACTH/MSH like peptides in the treatment of cisplatin neuropathy. 132 18

We report the results of a study of serum antibodies to proteins of the nerve cytoskeleton in patients with Type I and Type II diabetes mellitus, both with and without clinical signs of diabetic neuropathy. In contrast to previous reports, elevated levels of antibody to tubulin or glycated tubulin were not associated with either diabetes or diabetes with related neuropathy. Similarly, clinical evidence of neuropathy in patients with diabetes did not relate to increased levels of antibody to native or glycated microtubule-associated proteins (MAPs). The levels of antibody to MAPs and glycated MAPs were higher in control subjects over the age of 45 years compared with younger control subjects. Increased levels of antibody to tubulin and glycated tubulin were found in the sera of patients with systemic lupus erythematosus, but not rheumatoid arthritis.
Mol Chem Neuropathol 1991 Oct
PMID:Antibodies to tubulin and microtubule-associated proteins. A study in diabetes mellitus, systemic lupus erythematosus, and rheumatoid arthritis. 177 91

Diisopropyl phosphorofluoridate (DFP), an insecticide, is a potent anticholinesterase that binds essentially irreversibly to acetylcholinesterase, resulting in severe, acute neurologic pathology, and less severe, but longer-lasting, delayed neuropathy. We report here on the short-term effects of bath-applied DFP on extracellularly recorded responses from CA3 and CA1 of rat hippocampus. Exposure to 10 microM DFP evokes low amplitude, spontaneous bursts in CA3 generally within 10 minutes, and the bursting does not reverse with washing. The CA1 neuronal population usually bursts synchronously with CA3, but the population events are of low amplitude and sometimes not detectable, implying a differential sensitivity to DFP. These effects were partially blocked by the muscarinic antagonist atropine, while the cholinergic antagonist gallamine had little effect. Also, the reversible anticholinesterase physostigmine could, within temporal limits, protect slices from DFP's effects, implicating the cholinergic system as the probable mediator in the first stages of DFP-induced epileptogenesis.
Mol Chem Neuropathol
PMID:Effects of diisopropyl phosphorofluoridate (DFP) on CA3 and CA1 responses in rat hippocampus. 209 78

During the reductive process in the tissues, the aerobes generate a number of oxidants. Unless these oxidants are reduced, oxidative damage and cell death would occur. Oxidation of plasma membrane lipids leads to autocatalytic chain reactions which eventually alter the permeability of the cell. The role of oxidative damage in the pathophysiology of diabetic complications and ischemic reperfusion injury of myocardium, especially the changes in the channel activity which may lead to arrhythmia have been studied. Hyperglycemia activates aldose reductase which could efficiently reduce glucose to sorbitol in the presence of NADPH. Since NADPH is also aldose required by glutathione reductase for reducing oxidants, its diversion would lead to membrane lipid oxidation and permeability changes which are probably responsible for diabetic complications such as cataractogenesis, retinopathy, neuropathy etc. Antioxidants such as butylated hydroxy toluene (BHT) and also reductase inhibitors prevent or delay some of these complications. By using patch-clamp technique in isolated frog myocytes, we have shown that hydroxy radicals generated by ferrous sulfate and ascorbate as well as lipid peroxides such as t-butyl hydroperoxide facilitate the entry of Na+ by oxidizing Na+-channels. Increased intracellular Na+ leads to an increase in Na+/Ca2+ exchange. The increased Na+ concentration by itself may produce electrical disturbance which would result in arrhythmia. Increased Ca2+ may affect proteases and may help in the conversion of xanthine dehydrogenase to xanthine oxidase, consequently increased production of super oxide radicals. Increased membrane lipid peroxidation and other oxygen free-radical associated membrane damage in myocytes has been demonstrated.
Mol Cell Biochem
PMID:The effect of oxidants on biomembranes and cellular metabolism. 251 41

The neurotoxic gamma-diketone, 2,5-hexanedione, reacts with axonal protein amine residues to form 2,5-dimethylpyrrole adducts. Current evidence implicates this reaction as the potentially critical step in gamma-diketone neurotoxicity, although it is unclear whether pyrrole formation per se is sufficient to induce neuropathy or whether secondary autoxidative reactions are also required. The present in vitro study examines aspects of pyrrole formation and the secondary phenomena of chromophore development and covalent protein crosslinking in 2,5-hexanedione-treated protein. p-Dimethylaminobenzaldehyde (DMAB)-detectable pyrrole concentrations decreased linearly with time when pyrrolylated bovine serum albumin (pyrrole-BSA) was incubated under air, but remained unchanged following N2 incubation. The air-induced decrease was accompanied by the appearance of chromophores and crosslinked protein. Covalent crosslinking of pyrrole-BSA was pH-dependent, with relatively increased intermolecular bridging at pH 7.4 as compared to pH 9.5. Chromophore formation and the loss in DMAB-detectable pyrrole were also accelerated at the lower pH. Autoxidative parameters were inhibited in the presence of a free radical scavenger (ascorbic acid) but induced by free radical initiators (potassium persulfate and 2,2'-azobis[2-amidinopropane hydrochloride]). In vitro incubation followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of combinations of bovine serum albumin, ribonuclease, pyrrole-BSA, and pyrrolylated ribonuclease revealed that the intermolecular crosslinking pathway was mediated by pyrrole-pyrrole bridging. These findings demonstrate that the secondary autoxidative phenomena following pyrrole adduct formation in gamma-diketone-treated protein proceed via pH-dependent, free radical-mediated mechanisms. If similar mechanisms are present in vivo, the results also suggest that intermolecular covalent crosslinking of pyrrolylated axonal protein may be less widespread and more specific than previously thought.
Mol Pharmacol 1986 Nov
PMID:Mechanisms of in vitro pyrrole adduct autoxidation in 2,5-hexanedione-treated protein. 377 83

P0, the major structural protein of peripheral myelin, is a homophilic adhesion molecule with a single immunoglobulin (Ig) domain, which contains a single N-linked glycosylation site and two cysteines. We have previously reported four different mutations of the myelin P0 gene in four families of Charcot-Marie-Tooth neuropathy type 1 (CMT1). In this study we found a new mutation of the myelin P0 gene in a small family of CMT1. The affected persons had an A - to - G substitution of nucleotide 245 of the myelin P0 gene in one allele, leading to a cysteine substitution for tyrosine82 in the extracellular Ig-domain. An additional cysteine in the extracellular domain may form a disulfide bond and cause an inappropriate change in the tertiary structure of the functional Ig-domain of P0.
Biochem Mol Biol Int 1993 Sep
PMID:New mutation of the myelin P0 gene in a pedigree of Charcot-Marie-Tooth neuropathy 1. 750 51

We have previously reported that the mutations of the myelin P0 gene were completely linked with Charcot-Marie-Tooth neuropathy type 1B (CMT1B) in two families. In this study we found a different mutation in another family with CMT1B. The mutation, a methionine substitution for isoleucine at amino acid position 30, is located in the extracellular domain, which constitutes an immunoglobulin domain responsible for the function of P0 as an adhesion molecule. The results confirmed that P0 is a gene responsible for CMT1B.
Hum Mol Genet 1993 Sep
PMID:Mutation of the myelin P0 gene in Charcot-Marie-Tooth neuropathy type 1B. 769 26


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