Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.64 (MPP)
 1,876 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytochrome-c reductase (EC 1.10.2.2.) from Solanum tuberosum L. comprises ten subunits with apparent molecular sizes of 55, 53, 51, 35, 33, 25, 14, 12, 11 and 10 kDa on 14% SDS-PAGE. The identity of the subunits was analysed by direct amino-acid sequencing via cyclic Edman degradation. A large-scale purification procedure for the enzyme complex based on affinity chromatography and gelfiltraton is described. All subunits were enzymatically fragmented and the generated peptides were separated by reverse-phase HPLC. Complete or partial sequence determination of 33 peptides comprising a total of nearly 500 amino acids showed, that cytochrome-c reductase from potato contains three respiratory proteins (cytochrome b, cytochrome c1, and the "Rieske" iron-sulfur protein), four small proteins with molecular sizes below 15 kDa (so-called Q-binding, hinge, cytochrome-c1-linked and core-linked proteins) and three proteins in the 50-kDa range which show similarity to members of the core/PEP/MPP protein family (core/processing enhancing protein/mitochondrial processing peptidase). In fact these subunits show highest sequence identity either to MPP or PEP, which is in line with earlier findings, that isolated cytochrome-c reductase from potato exhibits processing activity towards mitochondrial precursor proteins.
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PMID:Molecular identification of the ten subunits of cytochrome-c reductase from potato mitochondria. 776 24

As the first step for production of rat apolipoprotein E (rApoE) in Saccharomyces cerevisiae, the rApoE cDNA was cloned and its nucleotide sequence was determined. When the intact rApoE gene including the presequence-encoding region was expressed under the control of the yeast GAL7 promoter, no protein immunoreactive with anti-rApoE antibody was detected either in the culture medium or inside the cells. For the purpose of the extracellular production of rApoE, three fusion genes were constructed in which the mature rApoE-encoding sequence was connected after the pre, prepro, and whole regions of the gene encoding a fungal aspartic proteinase, Mucor pusillus rennin (MPP), since MPP is efficiently secreted from recombinant S. cerevisiae containing the MPP gene. When these three fusion genes were expressed under the control of the GAL7 promoter, only one, encoding the mature rApoE connected to the whole MPP sequence, directed efficient secretion of the fused protein. The maximum yield of the fused protein secreted into the medium reached 11.8 mg/l and the calculated rApoE part was 5.3 mg in the fused protein. The excreted fusion protein was glycosylated at the original two sites in the MPP part. The fused protein was gradually degraded in the medium probably by proteases of the host cell, because no such degradation occurred in a yeast pep4mutant strain.
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PMID:Secretion by Saccharomyces cerevisiae of rat apolipoprotein E as a fusion to Mucor rennin. 776 86

Cytochrome c reductase from potato is a bifunctional protein complex located in the inner mitochondrial membrane, which is involved in respiratory electron transport and processing of mitochondrial precursor proteins. The three largest subunits of the complex share the highest degree of sequence identity with the alpha- and beta-subunits of the soluble processing peptidase (MPP) from fungi and mammals. Evidence is provided that another substoichiometric polypeptide of the cytochrome c reductase complex resembles the alpha-subunit of MPP. A cDNA clone corresponding to the second alpha-MPP protein (alpha-II MPP) encodes a polypeptide of 504 amino acids which is 84% identical to alpha-I MPP. The two different alpha-MPP polypeptides have similar sizes on SDS-polyacrylamide gels but can be distinguished with an antibody raised against a decapeptide that is specific for alpha-II MPP. The presequences of both alpha-subunits of MPP are proteolytically removed by the integrated processing enzyme complex indicating that it acts on the targeting signals of its own precursor proteins. Gene-specific oligonucleotides reveal that the genes encoding alpha-subunit I and alpha-subunit II of MPP are differentially expressed in all tissues analysed but the transcript levels do not vary between tissues.
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PMID:The mitochondrial processing peptidase from potato: a self-processing enzyme encoded by two differentially expressed genes. 781 32

1-Methyl-4-phenylpyridinum (MPP+), a selective neurotoxin, destroys the dopaminergic nigrostriatal pathway and results in a parkinsonian syndrome. Exposure of differentiated PC12 cells with nerve growth factor for 5 days to MPP+ (100 microM) for 4 h induced DNA fragmentation which is typical for the programmed cell death. MPP+ treatment (100 microM) concomitantly stimulates S6 kinase activity and resultant phosphorylation of S6 protein of 40S ribosomal subunits in the cells. Cycloheximide treatment prevents the MPP(+)-induced DNA fragmentation and enhancement of the phosphorylation of S6 protein. The present data demonstrate that neurotoxin, MPP+, kills differentiated PC12 cells by the apparent involvement of apoptotic process. Furthermore, the data strongly suggest that a change in protein phosphorylation might be involved in the signal transduction of MPP+ neurotoxicity and/or the protection from its toxicity.
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PMID:1-Methyl-4-phenylpyridinum kills differentiated PC12 cells with a concomitant change in protein phosphorylation. 783 84

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), an inducer of parkinsonism, causes degeneration of nigro-striatal dopaminergic neurons by producing its neurotoxic metabolite, 1-methyl-4-phenylpiridium ion (MPP+), by monoamine oxidase B in glial cells. We used PC12 (rat pheochromocytoma cell line) as a model cell line of dopamine-containing neurons and investigated the effects of various drugs on MPP(+)-induced cell death in PC12 cells. To estimate the cell death, we measured lactate dehydrogenase (LDH) activity leaked into the culture medium from damaged cells. When PC12 cells were treated with MPP+ at 0.3, 1.0 and 3.0 mM for 24 h, MPP+ increased the leakage of LDH and the leakage by 1.0 and 3.0 mM MPP+ was significant compared to the control. High K+ (50 mM KCl) significantly inhibited both MPP(+)-induced leakage of LDH and [3H]MPP+ uptake into the cells, suggesting that high K+ inhibits MPP(+)-induced cell death by inhibition of MPP+ uptake. NGF, dibutyryl cAMP (diBu-cAMP), cycloheximide (CHX) and aurintricarboxylic acid (ATA) significantly inhibited MPP(+)-induced leakage of LDH but did not inhibit [3H]MPP+ uptake, suggesting that these drugs inhibit MPP(+)-induced cell death at other sites than the one of MPP+ uptake.
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PMID:1-Methyl-4-phenylpyridinium (MPP+)-induced cell death in PC12 cells: inhibitory effects of several drugs. 784 70

Earlier studies from our laboratory have demonstrated that 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity could be modulated by inhibitors and inducer of cytochrome P450 (P450) in an in vitro model consisting of sagittal slices of mouse brain. To understand the molecular mechanisms underlying the role of P450 on MPTP toxicity, it was undertaken to study the effect of the modulators of P450 on the toxicity of the metabolite of MPTP, namely, 1-methyl-4-phenylpyridinium ion (MPP+). Incubation of mouse brain slices with various concentrations of MPP+ (1-100 microM) resulted in dose-dependent inhibition of mitochondrial enzyme NADH-dehydrogenase (NADH-DH) and leakage of the cytosolic enzyme lactate dehydrogenase from the slice into the medium. MPP(+)-induced toxicity was abolished by pretreatment of the slices with inhibitors of monoamine oxidase (MAO; pargyline and deprenyl) or inhibitors of P450 (piperonyl butoxide or SKF-525A) or dopamine uptake blocker (GBR-12909), as measured by the activity of NADH-DH in slices and leakage of lactate dehydrogenase from the slice into the medium. Slices prepared from mice pretreated with phenobarbital (an inducer of P450) potentiated the toxic effects of MPP+. Pretreatment of slices with MAO-inhibitor, P450 inhibitors, or dopamine uptake blocker attenuated the uptake of MPP+ into the slices. In contrast, MPP+ uptake was significantly increased in slices prepared from phenobarbital-pretreated mice. Thus, both MAO and P450 inhibitors abolish the toxicity of MPP+ in the sagittal slices of mouse brain by altering the uptake of the toxin into the slices.
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PMID:Protection and potentiation of 1-methyl-4-phenylpyridinium-induced toxicity by cytochrome P450 inhibitors and inducer may be due to the altered uptake of the toxin. 786 Nov 52

Superfusion of the rat striatum with 100 microM of 1-methyl-4-phenylpyridinium (MPP+) induced a 70-fold increase in dopamine (DA) release and a decrease in the extracellular levels of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). Pretreatment with riluzole (8 mg kg-1, i.p.), a compound that interferes with glutamatergic transmission, partially antagonized the effect of MPP+ on the release of DA, but did not change the effects of this toxin on the efflux of DOPAC and HVA. Riluzole did not affect the increase in DA release induced by MPP+ in vitro. The in vivo efficacy of riluzole on MPP(+)-induced DA release could be due to its central interference with glutamatergic transmission. Our data point to a protective role of riluzole with regard to DA release, a marker of the neuronal impairment induced by MPP+, a pro-parkinsonian neurotoxin.
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PMID:Riluzole and experimental parkinsonism: partial antagonism of MPP(+)-induced increase in striatal extracellular dopamine in rats in vivo. 786 66

N-methyl-4-phenylpyridinium (MPP+), the neurotoxic metabolite of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, kills dopaminergic neurons after its accumulation in mitochondria where it inhibits Complex I of the respiratory chain. MPP+ inhibits respiration by binding to both a hydrophobic and a hydrophilic site on Complex I and this inhibition is increased by the lipophilic tetraphenylboron anion (TPB-) which facilitates movement of MPP+ through membranes and its penetration to the hydrophobic binding site on Complex I. To investigate the inhibition of respiration by MPP(+)-like compounds, we have measured simultaneously NADH-linked mitochondrial respiration and the uptake and accumulation of the N-benzyl-4-styrylpyridinium and N-ethyl-4-styrylpyridinium cations in mitochondria using ion-selective electrodes. The data provide direct evidence that TPB- increases the inhibition not by increasing matrix concentration but by facilitating access to the inhibitory sites on Complex I. We have also compared the rates of uptake of MPP+ analogues of varied lipophilicity by the inner membrane and the development of inhibition of NADH oxidation, using an inverted mitochondrial inner membrane preparation and appropriate ion-selective electrodes. These experiments demonstrated that the amount of MPP+ analogue bound to the inner membrane greatly exceeded the quantity required for complete inhibition of NADH oxidation. Moreover, binding to the membrane occurred much more rapidly than the development of inhibition with all MPP+ analogues tested. This suggests that the attainment of a correct orientation of these compounds within the membrane and the binding site may be a rate-limiting step in the development of inhibition.
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PMID:Inhibition of complex I by hydrophobic analogues of N-methyl-4-phenylpyridinium (MPP+) and the use of an ion-selective electrode to measure their accumulation by mitochondria and electron-transport particles. 788 89

Selegiline was added to co-cultures of mesencephalon and neostriatum of C57BL/6 mouse embryos according to three schemes: (i) before and (ii) after cells were exposed to the toxin 1-methyl-4-phenylpyridinium (MPP+), (iii) in control cultures. In all schemes, selegiline enhanced the morphological differentiation of dopaminergic neurons and with delayed treatment, significantly increased their survival. These results indicate that selegiline exhibits trophic-like actions and can rescue MPP(+)-injured dopaminergic neurons in cultures.
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PMID:Selegiline enhances survival and neurite outgrowth of MPP(+)-treated dopaminergic neurons. 789 66

Serotonin antibodies (SAb) were found in the blood sera of middle-aged and elderly parkinsonian patients. The incidence of Sab in young and middle-aged healthy subjects was less, but increasing with age. Injected into the rabbit caudate nuclei, Sab suppressed the main pathogenetic mechanism of parkinsonian syndrome, the generator of pathologically enhanced excitation (GPEE) and parkinsonian symptoms induced by the MPP injection into substantia nigra. The intracaudate injection of serotonin enhanced GPEE activity and parkinsonian syndrome. The role of serotoninergic system and Sab in parkinsonism is discussed.
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PMID:[Serotonin antibodies and their possible role in parkinsonism]. 790 Apr 44


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