1-Methyl-4-phenylpyridinium: An active neurotoxic metabolite of 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE. The compound reduces dopamine levels, inhibits the biosynthesis of catecholamines, depletes cardiac norepinephrine and inactivates tyrosine hydroxylase. These and other toxic effects lead to cessation of oxidative phosphorylation, ATP depletion, and cell death. The compound, which is related to PARAQUAT, has also been used as an herbicide.1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine: A dopaminergic neurotoxic compound which produces irreversible clinical, chemical, and pathological alterations that mimic those found in Parkinson disease.MPTP Poisoning: A condition caused by the neurotoxin MPTP which causes selective destruction of nigrostriatal dopaminergic neurons. Clinical features include irreversible parkinsonian signs including rigidity and bradykinesia (PARKINSON DISEASE, SECONDARY). MPTP toxicity is also used as an animal model for the study of PARKINSON DISEASE. (Adams et al., Principles of Neurology, 6th ed, p1072; Neurology 1986 Feb;36(2):250-8)Organic Cation Transport Proteins: A family of proteins involved in the transport of organic cations. They play an important role in the elimination of a variety of endogenous substances, xenobiotics, and their metabolites from the body.Organic Cation Transporter 1: An organic cation transporter found in kidney. It is localized to the basal lateral membrane and is likely to be involved in the renal secretion of organic cations.Pyridinium CompoundsVesicular Biogenic Amine Transport Proteins: Integral membrane proteins of the LIPID BILAYER of SECRETORY VESICLES that catalyze transport and storage of biogenic amine NEUROTRANSMITTERS such as ACETYLCHOLINE; SEROTONIN; MELATONIN; HISTAMINE; and CATECHOLAMINES. The transporters exchange vesicular protons for cytoplasmic neurotransmitters.Rotenone: A botanical insecticide that is an inhibitor of mitochondrial electron transport.Herbicides: Pesticides used to destroy unwanted vegetation, especially various types of weeds, grasses (POACEAE), and woody plants. Some plants develop HERBICIDE RESISTANCE.Catecholamine Plasma Membrane Transport Proteins: A group of membrane transport proteins that transport biogenic amine derivatives of catechol across the PLASMA MEMBRANE. Catecholamine plasma membrane transporter proteins regulate neural transmission as well as catecholamine metabolism and recycling.Neurotoxins: Toxic substances from microorganisms, plants or animals that interfere with the functions of the nervous system. Most venoms contain neurotoxic substances. Myotoxins are included in this concept.Dopamine Agents: Any drugs that are used for their effects on dopamine receptors, on the life cycle of dopamine, or on the survival of dopaminergic neurons.Equilibrative Nucleoside Transport Proteins: A class of sodium-independent nucleoside transporters that mediate the facilitative transport of NUCLEOSIDES.Dopamine: One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.Parkinson Disease, Secondary: Conditions which feature clinical manifestations resembling primary Parkinson disease that are caused by a known or suspected condition. Examples include parkinsonism caused by vascular injury, drugs, trauma, toxin exposure, neoplasms, infections and degenerative or hereditary conditions. Clinical features may include bradykinesia, rigidity, parkinsonian gait, and masked facies. In general, tremor is less prominent in secondary parkinsonism than in the primary form. (From Joynt, Clinical Neurology, 1998, Ch38, pp39-42)Dopaminergic Neurons: Neurons whose primary neurotransmitter is DOPAMINE.Vesicular Monoamine Transport Proteins: A family of vesicular amine transporter proteins that catalyze the transport and storage of CATECHOLAMINES and indolamines into SECRETORY VESICLES.Tetrabenazine: A drug formerly used as an antipsychotic and treatment of various movement disorders. Tetrabenazine blocks neurotransmitter uptake into adrenergic storage vesicles and has been used as a high affinity label for the vesicle transport system.Mesencephalon: The middle of the three primitive cerebral vesicles of the embryonic brain. Without further subdivision, midbrain develops into a short, constricted portion connecting the PONS and the DIENCEPHALON. Midbrain contains two major parts, the dorsal TECTUM MESENCEPHALI and the ventral TEGMENTUM MESENCEPHALI, housing components of auditory, visual, and other sensorimoter systems.Monoamine Oxidase: An enzyme that catalyzes the oxidative deamination of naturally occurring monoamines. It is a flavin-containing enzyme that is localized in mitochondrial membranes, whether in nerve terminals, the liver, or other organs. Monoamine oxidase is important in regulating the metabolic degradation of catecholamines and serotonin in neural or target tissues. Hepatic monoamine oxidase has a crucial defensive role in inactivating circulating monoamines or those, such as tyramine, that originate in the gut and are absorbed into the portal circulation. (From Goodman and Gilman's, The Pharmacological Basis of Therapeutics, 8th ed, p415) EC 1.4.3.4.Dopamine Plasma Membrane Transport Proteins: Sodium chloride-dependent neurotransmitter symporters located primarily on the PLASMA MEMBRANE of dopaminergic neurons. They remove DOPAMINE from the EXTRACELLULAR SPACE by high affinity reuptake into PRESYNAPTIC TERMINALS and are the target of DOPAMINE UPTAKE INHIBITORS.3,4-Dihydroxyphenylacetic Acid: A deaminated metabolite of LEVODOPA.Parkinson Disease: A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75)Membrane Transport Proteins: Membrane proteins whose primary function is to facilitate the transport of molecules across a biological membrane. Included in this broad category are proteins involved in active transport (BIOLOGICAL TRANSPORT, ACTIVE), facilitated transport and ION CHANNELS.Parkinsonian Disorders: A group of disorders which feature impaired motor control characterized by bradykinesia, MUSCLE RIGIDITY; TREMOR; and postural instability. Parkinsonian diseases are generally divided into primary parkinsonism (see PARKINSON DISEASE), secondary parkinsonism (see PARKINSON DISEASE, SECONDARY) and inherited forms. These conditions are associated with dysfunction of dopaminergic or closely related motor integration neuronal pathways in the BASAL GANGLIA.Cations: Positively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis.Substantia Nigra: The black substance in the ventral midbrain or the nucleus of cells containing the black substance. These cells produce DOPAMINE, an important neurotransmitter in regulation of the sensorimotor system and mood. The dark colored MELANIN is a by-product of dopamine synthesis.Tyrosine 3-Monooxygenase: An enzyme that catalyzes the conversion of L-tyrosine, tetrahydrobiopterin, and oxygen to 3,4-dihydroxy-L-phenylalanine, dihydrobiopterin, and water. EC 1.14.16.2.Neuroprotective Agents: Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but often directly or indirectly minimize the damage produced by endogenous excitatory amino acids.Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.PC12 Cells: A CELL LINE derived from a PHEOCHROMOCYTOMA of the rat ADRENAL MEDULLA. PC12 cells stop dividing and undergo terminal differentiation when treated with NERVE GROWTH FACTOR, making the line a useful model system for NERVE CELL differentiation.Biological Transport: The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments.Corpus Striatum: Striped GRAY MATTER and WHITE MATTER consisting of the NEOSTRIATUM and paleostriatum (GLOBUS PALLIDUS). It is located in front of and lateral to the THALAMUS in each cerebral hemisphere. The gray substance is made up of the CAUDATE NUCLEUS and the lentiform nucleus (the latter consisting of the GLOBUS PALLIDUS and PUTAMEN). The WHITE MATTER is the INTERNAL CAPSULE.Nerve Degeneration: Loss of functional activity and trophic degeneration of nerve axons and their terminal arborizations following the destruction of their cells of origin or interruption of their continuity with these cells. The pathology is characteristic of neurodegenerative diseases. Often the process of nerve degeneration is studied in research on neuroanatomical localization and correlation of the neurophysiology of neural pathways.Mitochondria: Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed)Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.NG-Nitroarginine Methyl Ester: A non-selective inhibitor of nitric oxide synthase. It has been used experimentally to induce hypertension.Reactive Oxygen Species: Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of signal transduction and gene expression, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS.
(1/255) Poly(ADP-ribose) polymerase activation mediates 1-methyl-4-phenyl-1, 2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin that causes parkinsonism in humans and nonhuman animals, and its use has led to greater understanding of the pathogenesis of Parkinson's disease. However, its molecular targets have not been defined. We show that mice lacking the gene for poly(ADP-ribose) polymerase (PARP), which catalyzes the attachment of ADP ribose units from NAD to nuclear proteins after DNA damage, are dramatically spared from MPTP neurotoxicity. MPTP potently activates PARP exclusively in vulnerable dopamine containing neurons of the substantia nigra. MPTP elicits a novel pattern of poly(ADP-ribosyl)ation of nuclear proteins that completely depends on neuronally derived nitric oxide. Thus, NO, DNA damage, and PARP activation play a critical role in MPTP-induced parkinsonism and suggest that inhibitors of PARP may have protective benefit in the treatment of Parkinson's disease.  (+info)

(2/255) Comparison of the pharmacological properties of cloned rat, human, and bovine norepinephrine transporters.

The aims of this study were to characterize the recently cloned rat norepinephrine transporter (NET) in more detail and in particular to study possible species differences in its pharmacological properties compared with the human and bovine NETs. The study was carried out by measuring the uptake of [(3)H]norepinephrine in COS-7 cells expressing the NET after transient transfection with rat, human, or bovine NET cDNA. There were small but significant differences between the rat NET and the human or bovine NETs with respect to the affinities of sodium ions (greater for rat than for bovine) of the substrates norepinephrine, epinephrine, and 1-methyl-4-phenylpyridinium (greater for human than for rat), and of the inhibitor cocaine (greater for human and bovine than for rat), whereas the affinities of dopamine and of most inhibitors, including tricyclic antidepressants, showed no species differences. The fact that the affinities for some substrates, cocaine and sodium ions exhibited small but significant interspecies differences among the rat, human, and bovine NETs suggests that ligand recognition, the translocation process, and sodium ion dependence are influenced differentially by just a few amino acid exchanges in the primary sequences of the transporters. On the other hand, the lack of any major differences in the pharmacological properties of the rat, human, and bovine NETs in this study suggests that data obtained in previous studies on rat tissues and bovine cells can be extrapolated, in all except the most quantitative analyses, to the properties of the human NET.  (+info)

(3/255) LLC-PK(1) cells stably expressing the human norepinephrine transporter: A functional model of carrier-mediated norepinephrine release in protracted myocardial ischemia.

In myocardial ischemia, adrenergic terminals undergo ATP depletion, hypoxia, and intracellular pH reduction, causing the accumulation of axoplasmic norepinephrine (NE) and intracellular Na(+) [via the Na(+)-H(+) exchanger (NHE)]. This forces the reversal of the Na(+)- and Cl(-)-dependent NE transporter (NET), triggering massive carrier-mediated NE release and, thus, arrhythmias. We have now developed a cellular model of carrier-mediated NE release using an LLC-PK(1) cell line stably transfected with human NET cDNA (LLC-NET). LLC-NET cells transported [(3)H]NE and [(3)H]N-methyl-4-phenylpyridinium ([(3)H]MPP(+)) in an inward direction. This uptake was abolished by the NET inhibitors desipramine (100 nM) and mazindol (300 nM) and by extracellular Na(+) removal. Na(+)-gradient reversal induced an efflux of (3)H-substrate from preloaded LLC-NET cells. Desipramine and mazindol blocked this efflux. Because of its greater intracellular stability and higher sensitivity to Na(+)-gradient reversal, [(3)H]MPP(+) proved preferable to [(3)H]NE as an NET substrate; therefore, only [(3)H]MPP(+) was used for subsequent studies. The K(+)/H(+) ionophore nigericin (10 microM) evoked a large efflux of [(3)H]MPP(+). This efflux was potentiated by the Na(+),K(+)-ATPase inhibitor ouabain (100 microM), was sensitive to desipramine, and was blocked by the NHE inhibitor 5-(N-ethyl-N-isopropyl)-amiloride (EIPA; 10 microM). In contrast, EIPA failed to inhibit the [(3)H]MPP(+) efflux elicited by the Na(+) ionophore gramicidin (10 microM). Furthermore, [(3)H]MPP(+) efflux induced by the NHE-stimulant proprionate (25 mM) was negatively modulated by imidazoline receptor activation. Our findings suggest that LLC-NET cells are a sensitive model for studying transductional processes of carrier-mediated NE release associated with myocardial ischemia.  (+info)

(4/255) Ion dependence of carrier-mediated release in dopamine or norepinephrine transporter-transfected cells questions the hypothesis of facilitated exchange diffusion.

The mechanism of release mediated by the human dopamine and norepinephrine transporter (DAT and NET, respectively) was studied by a superfusion technique in human embryonic kidney 293 cells stably transfected with the respective transporter cDNA and loaded with the metabolically inert substrate [(3)H]1-methyl-4-phenylpyridinium. Release was induced by amphetamine, dopamine, and norepinephrine or by lowering the sodium or chloride concentration in the superfusion buffer (iso-osmotic replacement by lithium and isethionate, respectively). Efflux of [(3)H]1-methyl-4-phenylpyridinium was analyzed at 30-s time resolution. In both transporters, release induced by the substrates amphetamine, dopamine, and norepinephrine followed the same time course as release induced by the removal of chloride and was faster than that caused by the removal of sodium. In the presence of low sodium (DAT: 10 mM; NET: 5 mM) none of the substrates was able to induce release from either type of cell, but adding back sodium to control conditions promptly restored the releasing action. In the presence of low chloride (DAT: 3 mM; NET: 2 mM), however, amphetamine as well as the catecholamines stimulated release from both types of cell. In contrast with the ion dependence of release observed in superfusion experiments, uptake initial rates of substrates at concentrations used in release experiments were the same or even higher at low sodium than at low chloride. The results indicate a decisive role of extracellular sodium for carrier-mediated release unrelated to the sodium-dependent uptake of the releasing substrate, and suggest a release mechanism different from simple exchange diffusion considering only the amines as substrates.  (+info)

(5/255) 1-Methyl-4-phenyl-2,3-dihydropyridinium is transformed by ubiquinone to the selective nigrostriatal toxin 1-methyl-4-phenylpyridinium.

We have studied the interaction of coenzyme Q with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its metabolites, 1-methyl-4-phenyl-2,3-dihydropyridinium (MPDP(+)) and 1-methyl-4-phenylpyridinium (MPP(+)), the real neurotoxin to cause Parkinson's disease. Incubation of MPTP or MPDP(+) with rat brain synaptosomes induced complete reduction of endogenous ubiquinone-9 and ubiquinone-10 to corresponding ubiquinols. The reduction occurred in a time- and MPTP/MPDP(+) concentration-dependent manner. The reduction of ubiquinone induced by MPDP(+) went much faster than that by MPTP. MPTP did not reduce liposome-trapped ubiquinone-10, but MPDP(+) did. The real toxin MPP(+) did not reduce ubiquinone in either of the systems. The reduction by MPTP but not MPDP(+) was completely prevented by pargyline, a type B monoamine oxidase (MAO-B) inhibitor, in the synaptosomes. The results indicate that involvement of MAO-B is critical for the reduction of ubiquinone by MPTP but that MPDP(+) is a reductant of ubiquinone per se. It is suggested that ubiquinone could be an electron acceptor from MPDP(+) and promote the conversion from MPDP(+) to MPP(+) in vivo, thus accelerating the neurotoxicity of MPTP.  (+info)

(6/255) The D-loop structure of human mtDNA is destabilized directly by 1-methyl-4-phenylpyridinium ion (MPP+), a parkinsonism-causing toxin.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine has been reported to cause parkinsonism via its neurotoxic form, 1-methyl-4-phenylpyridinium ion (MPP+), which inhibits complex I of the mitochondrial respiratory chain. Its parkinsonism-causing mechanisms attract a great deal of interest as a model of the disease. Recently, we reported that MPP+ strongly decreases the amount of mtDNA independent of the inhibition of complex I. Maintenance of a proper amount of mtDNA is essential for the normal function of mitochondria as exemplified in many mitochondrial diseases. The most characteristic feature in vertebral mtDNA replication is that H-strand synthesis proceeds displacing the parental H-strand as a long single strand. It forms the D-loop, a triplex replication intermediate composed of the parental L-strand, nascent H-strand and displaced H-strand. Here we show that MPP+ does not inhibit DNA synthesis by DNA polymerase gamma, but rather releases the nascent H-strands from mtDNA both in organello and in vitro. This indicates that MPP+ directly destabilizes the D-loop structure, thereby inhibiting replication. This study raises a new mechanism, i.e. destabilization of replication intermediates, for depletion of mtDNA.  (+info)

(7/255) Kinetic and selectivity differences between rodent, rabbit, and human organic cation transporters (OCT1).

Organic cation transporters play an important role in the absorption, distribution, and elimination of clinical agents, toxic substances, and endogenous compounds. In kidney preparations, significant differences in functional characteristics of organic cation transport between various species have been reported. However, the underlying molecular mechanisms responsible for these interspecies differences are not known. The goal of this study was to determine the kinetics and substrate selectivities of organic cation transporter (OCT1) homologs from mouse, rat, rabbit, and human that may contribute to interspecies differences in the renal and hepatic handling of organic cations. With a series of n-tetraalkylammonium (nTAA) compounds, a correlation between increasing alkyl chain length and affinity for the four OCT1 homologs was observed. However, the apparent affinity constants (K(i)) differed among the species homologs. For the mouse homolog mOCT1, apparent K(i) values ranged from 7 microM for tetrabutylammonium to 2000 microM for tetramethylammonium. In contrast, the human homolog hOCT1 exhibited weaker interactions with the nTAA compounds. Trans-stimulation studies and current measurements in voltage-clamped oocytes demonstrated that larger nTAA compounds were transported at greater rates in oocytes expressing hOCT1, whereas smaller nTAAs were transported at greater rates in oocytes expressing mOCT1 or rOCT1. The rabbit homolog rbOCT1 exhibited intermediate properties in its interactions with nTAAs compared with its rodent and human counterparts. This report demonstrates that the human OCT1 homolog has functional properties distinct from those of the rodent and rabbit OCT1 homologs. The study underscores potential difficulties in extrapolating data from preclinical studies in animal models to humans.  (+info)

(8/255) Characterization of MPP+ secretion across human intestinal Caco-2 cell monolayers: role of P-glycoprotein and a novel Na(+)-dependent organic cation transport mechanism.

1. In the kidney, a number of transport proteins involved in the secretion of permanently charged organic cations have recently been cloned. To evaluate the possible similarities between intestine and kidney in the handling of organic cations we investigated the transport of 1-methyl-4-phenylpyridinium (MPP+) across monolayers of intestinal Caco-2 cells. MPP+ is a prototypic substrate of the cloned organic cation transporters hOCT1 and hOCT2. 2. In Caco-2 cell monolayers, the basolateral to apical flux of MPP+ was significantly greater than the apical to basolateral flux, consistent with net secretion of MPP+. 3. Net secretion of MPP+ was abolished by addition of either 10 microM cyclosporin A or 100 microM verapamil to the apical membrane. In contrast, secretion of MPP+ was unaffected by addition of either TEA (2 mM) or decynium-22 (2 microM) to either apical or basolateral membranes. These results suggest that MPP+ secretion is mediated primarily by P-glycoprotein located at the apical membrane. We found no evidence of a role for hOCT1 or hOCT2 in the secretion of MPP+. 4. In addition to net secretion of MPP+, we found evidence of a Na(+)-dependent MPP+ uptake mechanism at the apical membrane of Caco-2 cells. 5. Na(+)-dependent MPP+ uptake was sensitive to inhibition by the organic cations; decynium-22 (2 microM), TEA (2 mM) and cimetidine (5 mM) but not by carnitine, guanidine or proline. 6. These results suggest that net secretion of MPP+ across the apical membrane of Caco-2 cells is a function of the relative contributions of MPP+ secretion mediated by P-glycoprotein and MPP+ absorption mediated by a novel Na(+)-dependent transport mechanism.  (+info)

*  Vesicular monoamine transporter
Phenylethylamine Amphetamine MDMA N-methyl-4-phenylpyridinium (MPP+)(very potent inhibitors of VMAT2 mediated serotonin ... 31 (4): 483-19. doi:10.1002/med.20187. PMC 3019297 . PMID 20135628. Liu Y, Peter D, Rogahani A, Schuldiner S, Prive GG, ... 31 (4): 483-519. doi:10.1002/med.20187. PMC 3019297 . PMID 20135628. Henry J. P.; Botton D.; et al. (1994). "Biochemistry and ... VMAT gene sequence analysis demonstrates that 4 aspartic acid residues in the middle region of TMD I, VI, X, and XI and one ...
*  MPP+
... (1-methyl-4-phenylpyridinium) is a positively charged molecule with chemical formula C12H12N+. It is toxic and acts by ... 126 (4): 529-40. doi:10.1111/jnc.12228. PMC 3737274 . PMID 23452092. Jeong, Kyoung Hoon; Jeon, Min-Tae; Kim, Heung Deok; Jung, ... "Nobiletin Protects Dopaminergic Neurons in the 1-Methyl-4-Phenylpyridinium-Treated Rat Model of Parkinson's Disease". Journal ...
*  Annonacin
88 (1): 63-69. doi:10.1046/j.1471-4159.2003.02138.x. PMID 14675150. Yuan, S. S.; Chang, H. L.; Chen, H. W.; Yeh, Y. T.; Kao, Y ... 63 (4): 1053. doi:10.1021/jf504500g. PMID 25594104. Potts, L. F.; Luzzio, F. A.; Smith, S. C.; Hetman, M; Champy, P; Litvan, I ... doi:10.1385/1-59259-365-8:133 Lannuzel, A. and Michel, P. P. (2008). Atypical Parkinsonism in the French West Indies: The Plant ... 33 (1): 53-8. doi:10.1016/j.neuro.2011.10.009. PMID 22130466. Le Ven, J.; Schmitz-Afonso, I.; Touboul, D.; Buisson, D.; Akagah ...
*  Phosphoenolpyruvate carboxykinase
Accessed 10:46PM, 4/13/07. www.mc.vanderbilt.edu/root/vumc.php?site=granner&doc=119 Burgess SC, He T, Yan Z, Lindner J, Sherry ... 98 (1): 77-91. doi:10.1093/aob/mcl096. PMC 2803547 . PMID 16704997. Chen ZH, Walker RP, Técsi LI, Lea PJ, Leegood RC (May 2004 ... 1697 (1-2): 271-8. doi:10.1016/j.bbapap.2003.11.030. PMID 15023367. Trapani S, Linss J, Goldenberg S, Fischer H, Craievich AF, ... 59 (1): 105-13. doi:10.1016/j.jhep.2013.02.020. PMC 3910155 . PMID 23466304. Chakravarty K, Cassuto H, Reshef L, Hanson RW ( ...
*  William Langston
46 (4): 598-605. doi:10.1002/1531-8249(199910)46:4. 3.0.CO;2-F. PMID 10514096. Farrer M, Chan P, Chen R, Tan L, Lincoln S, ... 281 (4): 341-6. doi:10.1001/jama.281.4.341. PMID 9929087. Langston JW, Forno LS, Tetrud J, Reeves AG, Kaplan JA, Karluk D (Oct ... 59 (4): 591-6. doi:10.1002/ana.20834. PMID 16566021. Tanner CM, Ross GW, Jewell SA, Hauser RA, Jankovic J, Factor SA, Bressman ... 7 (1): 2-13. doi:10.1002/mds.870070103. PMID 1557062. Widner H, Tetrud J, Rehncrona S, Snow B, Brundin P, Gustavii B, Björklund ...
*  Desmethylprodine
Structural analogs of desmethylprodine with different N-substituents than a methyl group on the piperidine have been ... 13 (4): 367-374. doi:10.1016/0376-8716(84)90004-8. PMID 6148225. Davis, G. C.; Williams, A. C.; Markey, S. P.; Ebert, M. H.; ... Desmethylprodine or 1-methyl-4-phenyl-4-propionoxypiperidine (MPPP, Ro 2-0718) is an opioid analgesic drug developed in the ... It was later found that his development of Parkinson's was due to a common impurity in the synthesis of MPPP called MPTP (1- ...
*  Secalonic acid
In all known secalonic acids, the methyl and methoxycarbonyl substituents are found to be trans to each other, and X-ray ... 32 (1): 1-104. doi:10.1039/c4np00050a. PMID 25226564. Zhang W, Krohn K, Flörke U, Pescitelli G, Di Bari L, Antus S, Kurtán T, ... 713 (1-3): 58-67. doi:10.1016/j.ejphar.2013.04.029. ISSN 0014-2999. PMID 23665112. Millot M, Tomasi S, Studzinska E, Rouaud I, ... 58 (1): 85-91. doi:10.1016/j.neuint.2010.10.016. PMID 21073911. Zhai, Aifeng; Zhu, Xiaonan; Wang, Xuelan; Chen, Ruzhu; Wang, ...
*  Competitive inhibition
In the simplest case of a single-substrate enzyme obeying Michaelis-Menten kinetics, the typical scheme E + S ⇌ k − 1 k 1 ES → ... Cells in the central nervous system (astrocytes) include MAO-B that oxidizes MPTP to 1-methyl-4-phenylpyridinium (MPP+), which ... After an accidental ingestion of a contaminated opioid drug desmethylprodine, the neurotoxic effect of 1-methyl-4-phenyl-1,2,3, ... Competitive substrates, such as 4-substituted benzaldehydes for mushrooms, compete with the substrate lowering the amount of ...
*  Decynium-22
84 (1): 43-52. doi:10.1046/j.1471-4159.2003.01566.x. PMID 12485400. Stiel H, Daehne S, Teuchner K. J-aggregates of ... Decynium-22 has been shown to block the uptake of 1-methyl-4-phenylpyridinium (MPP) via the OCT3 transporter in rat astrocytes ... Dynamics of formation of 1,1′-diethyl-2,2′-cyanine iodide J-aggregates in solution. J Physical Chem A. 2000;104:9670-9674. ... 2010). "Membrane potential and pH-dependent accumulation of decynium-22 (1,1'-diethyl-2,2'-cyanine iodide) flourencence through ...
*  MPTP
... (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is a prodrug to the neurotoxin MPP+, which causes permanent symptoms of ... 1 (3): 249-254. doi:10.1016/0165-1781(79)90006-4. CS1 maint: Multiple names: authors list (link) "Success reported using fetal ... "1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine". ChemIDplus. Langston, J. W. (2002). "Chapter 30 The Impact of MPTP on ... 2 (1): 141-151. doi:10.1038/nprot.2006.342. PMID 17401348. "Pesticides and Parkinson's Disease - A Critical Review" (PDF). ...
*  List of MeSH codes (D03)
... methyl ester MeSH D03.383.725.547.950 --- xanthinol niacinate MeSH D03.383.725.565 --- nicotinyl alcohol MeSH D03.383.725.592 ... methyl ester MeSH D03.383.725.210 --- dimethindene MeSH D03.383.725.220 --- 2,2'-dipyridyl MeSH D03.383.725.227 --- ... 5-tetrahydro-8-chloro-3-methyl-5-phenyl-1h-3-benzazepin-7-ol MeSH D03.438.079.800 --- 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl ... alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid MeSH D03.383.129.385.162 --- cycloserine MeSH D03.383.129.385.231 --- ...
*  Soursop
1. Retrieved 2008-04-18. UBC Botanical Garden and Centre for Plant Research (2007-04-13). "Annona muricata". Botany Photo of ... Annona muricata is a small, upright, evergreen tree that can grow to about 4 metres (13 ft) tall. Its young branches are hairy ... The ovaries are covered with dense reddish brown hairs, 1-ovuled, style short and stigma truncate. The fruits are dark green ... The leaf stalks are 4 millimetres (0.16 in) to 13 millimetres (0.51 in) long and without hairs. Flower stalks (peduncles) are 2 ...
*  GOT2
27 (4): 1064-74. doi:10.1002/hep.510270423. PMID 9537447. Yang H, Zhou L, Shi Q, Zhao Y, Lin H, Zhang M, Zhao S, Yang Y, Ling ... 22 (1-6): 190-4. doi:10.1159/000130933. PMID 752471. Pol S, Bousquet-Lemercier B, Pavé-Preux M, Bulle F, Passage E, Hanoune J, ... 832 (1): 46-51. doi:10.1016/0167-4838(85)90172-4. PMID 4052435. Davidson RG, Cortner JA, Rattazzi MC, Ruddle FH, Lubs HA (Jul ... 138 (1-2): 171-4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298. Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano ...
*  Loperamide
"Identification of an N-Methyl-4-Phenylpyridinium-Like Metabolite of the Antidiarrheal Agent Loperamide in Human Liver ... 1, June 2011. Archived from the original (PDF) on 6 September 2014. Retrieved 2014-09-05. "The Selection and Use of Essential ... Ben Guarino (4 May 2016). "Abuse of diarrhea medicine you know well is alarming physicians". The Washington Post. Archived from ... 4, No. 2, 1990. 1990. pp. 73-74. Archived from the original (PDF) on 6 September 2014. Retrieved 2014-09-06. The leading ...
*  Phenethylamine
Phenylethylamine (10), amphetamine [AMPH (11 & 12)], methylenedioxy methamphetamine [METH (13)] and N-methyl-4-phenylpyridinium ... 4 (9). PMC 3904499 . PMID 24482732. While diagnosis of ADHD is usually done by analysis of the symptoms (American Psychiatric ... 16 (1): 9-18. doi:10.1016/0031-9422(77)83004-5. Irsfeld M, Spadafore M, Prüß BM; Spadafore; Prüß (September 2013). "β- ... 96 (1): 165-71. doi:10.1016/j.meatsci.2013.06.030. PMID 23896151. Acetoacetic acid (AAA) and ß-phenylethylamine (PEA) performed ...
Caspase-dependent and -independent cell death pathways in primary cultures of mesencephalic dopaminergic neurons after...  Caspase-dependent and -independent cell death pathways in primary cultures of mesencephalic dopaminergic neurons after...
... or 1-methyl-4-phenylpyridinium (MPP+) treatment. Both immunofluorescent labeling and immunoblot analysis indicated ... or 1-methyl-4-phenylpyridinium (MPP+) treatment. Both immunofluorescent labeling and immunoblot analysis indicated ... or 1-methyl-4-phenylpyridinium (MPP+) treatment. Both immunofluorescent labeling and immunoblot analysis indicated ... or 1-methyl-4-phenylpyridinium (MPP+) treatment. Both immunofluorescent labeling and immunoblot analysis indicated ...
more infohttps://yonsei.pure.elsevier.com/en/publications/caspase-dependent-and-independent-cell-death-pathways-in-primary-
eCite - Oxaliplatin transport mediated by organic cation/carnitine transporters OCTN1 and OCTN2 in overexpressing human...  eCite - Oxaliplatin transport mediated by organic cation/carnitine transporters OCTN1 and OCTN2 in overexpressing human...
... methyl-4-phenylpyridinium (MPP ) (OCT1 3), [14C]tetraethylammonium bromide (TEA ) (OCT1 3 and OCTN1/2), [3H]ergothioneine ( ... School of Nursing & Midwifery Education Centre, 1 Leichhardt St, Darlinghurst NSW 2010 T: +61 2 8382 4820 ...
more infohttp://ecite.utas.edu.au/86354
DLP1-dependent mitochondrial fragmentation mediates 1-methyl-4-phenylpyridinium toxicity in neurons: implications for Parkinson...  DLP1-dependent mitochondrial fragmentation mediates 1-methyl-4-phenylpyridinium toxicity in neurons: implications for Parkinson...
Wang X1, Su B, Liu W, He X, Gao Y, Castellani RJ, Perry G, Smith MA, Zhu X. ... Figure 4. MPP+ caused a rapid decrease in intracellular ATP levels and ATP/ADP ratio concurrent with enhanced mitochondrial ... The relative mito-DLP1 level was defined as the relative ratio (control is set as 1) between the intensity of green signal that ... 1. Department of Pathology, Case Western Reserve University, 2103 Connell Road, Cleveland, OH 44106, USA.. ...
more infohttps://www.ncbi.nlm.nih.gov/pubmed/21615675
Toxicity of the 1-methyl-4-phenyl-2,3-dihydropyridinium and 1-methyl-4-phenylpyridinium species in primary cultures of mouse...  Toxicity of the 1-methyl-4-phenyl-2,3-dihydropyridinium and 1-methyl-4-phenylpyridinium species in primary cultures of mouse...
Toxicity of the 1-methyl-4-phenyl-2,3-dihydropyridinium and 1-methyl-4-phenylpyridinium species in primary cultures of mouse ... Toxicity of the 1-methyl-4-phenyl-2,3-dihydropyridinium and 1-methyl-4-phenylpyridinium species in primary cultures of mouse ... Toxicity of the 1-methyl-4-phenyl-2,3-dihydropyridinium and 1-methyl-4-phenylpyridinium species in primary cultures of mouse ... Toxicity of the 1-methyl-4-phenyl-2,3-dihydropyridinium and 1-methyl-4-phenylpyridinium species in primary cultures of mouse ...
more infohttp://jpet.aspetjournals.org/content/262/1/225
Glia Maturation Factor Deficiency Suppresses 1-Methyl-4-Phenylpyridinium-Induced Oxidative Stress in Astrocytes - Semantic...  Glia Maturation Factor Deficiency Suppresses 1-Methyl-4-Phenylpyridinium-Induced Oxidative Stress in Astrocytes - Semantic...
... interleukin-1β (IL-1β), IL-17, IL-33, and chemokine (C-C motif) ligand 2 (CCL2) in GMF-KO astrocytes when compared to Wt ... along with diminished nuclear factor-κB-mediated inflammatory responses in 1-methyl-4-phenylpyridinium (MPP+)-induced toxicity ... Mast Cells Release Chemokine CCL2 in Response to Parkinsonian Toxin 1-Methyl-4-Phenyl-Pyridinium (MPP+). *Duraisamy Kempuraj, ... Dopaminergic Toxin 1-Methyl-4-Phenylpyridinium, Proteins α-Synuclein and Glia Maturation Factor Activate Mast Cells and Release ...
more infohttps://www.semanticscholar.org/paper/Glia-Maturation-Factor-Deficiency-Suppresses-Stress-Khan-Kempuraj/b337c34eefbc67054b7d95d3ed6a41711196b2ed
Rat Organic Cation Transporter 1 Contains Three Binding Sites for Substrate 1-Methyl-4-phenylpyridinium per Monomer | Molecular...  Rat Organic Cation Transporter 1 Contains Three Binding Sites for Substrate 1-Methyl-4-phenylpyridinium per Monomer | Molecular...
Rat Organic Cation Transporter 1 Contains Three Binding Sites for Substrate 1-Methyl-4-phenylpyridinium per Monomer. Thorsten ... Rat Organic Cation Transporter 1 Contains Three Binding Sites for Substrate 1-Methyl-4-phenylpyridinium per Monomer. Thorsten ... Rat Organic Cation Transporter 1 Contains Three Binding Sites for Substrate 1-Methyl-4-phenylpyridinium per Monomer. Thorsten ... Here we measured binding and transport of model substrate 1-methyl-4-phenylpyridinium+ (MPP+) by cell-free-expressed fusion ...
more infohttp://molpharm.aspetjournals.org/content/early/2018/11/08/mol.118.113498
Rat Organic Cation Transporter 1 Contains Three Binding Sites for Substrate 1-Methyl-4-phenylpyridinium per Monomer | Molecular...  Rat Organic Cation Transporter 1 Contains Three Binding Sites for Substrate 1-Methyl-4-phenylpyridinium per Monomer | Molecular...
Rat Organic Cation Transporter 1 Contains Three Binding Sites for Substrate 1-Methyl-4-phenylpyridinium per Monomer. Thorsten ... Rat Organic Cation Transporter 1 Contains Three Binding Sites for Substrate 1-Methyl-4-phenylpyridinium per Monomer ... Molecular Pharmacology February 1, 2019, 95 (2) 169-182; DOI: https://doi.org/10.1124/mol.118.113498 ... Molecular Pharmacology February 1, 2019, 95 (2) 169-182; DOI: https://doi.org/10.1124/mol.118.113498 ...
more infohttp://molpharm.aspetjournals.org/content/95/2/169/tab-e-letters
Formation of superoxide and hydroxyl radicals from 1-methyl-4-phenylpyridinium ion (MPP+): reductive activation by NADPH...  Formation of superoxide and hydroxyl radicals from 1-methyl-4-phenylpyridinium ion (MPP+): reductive activation by NADPH...
... methyl-4-phenylpyridinium ion(MPP+) has been studied using spin-trapping techniques. Incubation of MPP+ with purified NADPH ... methyl-4-phenylpyridinium ion(MPP+) has been studied using spin-trapping techniques. Incubation of MPP+ with purified NADPH ... DJ-1 Interacts with and Regulates Paraoxonase-2, an Enzyme Critical for Neuronal Survival in Response to Oxidative Stress. ... Modulation of apoptosis, tyrosine hydroxylase expression and 1-methyl-4-phenylpyridinium toxicity. María Angeles González Mena ...
more infohttps://www.semanticscholar.org/paper/Formation-of-superoxide-and-hydroxyl-radicals-from-Sinha-Singh/c33b41cbf1fd42654141a4ece7d704ee07969283
High-performance liquid chromatography/tandem mass spectrometry assay for the determination of 1-methyl-4-phenyl pyridinium ...  High-performance liquid chromatography/tandem mass spectrometry assay for the determination of 1-methyl-4-phenyl pyridinium ...
The limit of detection for MPP+ was found to be 1 fmol on column with a signal to noise ratio of 3:1. The assay has been used ... A high-throughput liquid chromatography/tandem mass spectrometry method has been developed for the quantitative assessment of 1 ... methyl-4-phenylpyridinium (MPP+) in brain tissue samples. This separation is based on reversed phase chromatography using ... High-performance liquid chromatography/tandem mass spectrometry assay for the determination of 1-methyl-4-phenyl pyridinium ( ...
more infohttp://eprints.mdx.ac.uk/22824/
Minocycline prevents nigrostriatal dopaminergic neurodegeneration in the MPTP model of Parkinsons disease | PNAS  Minocycline prevents nigrostriatal dopaminergic neurodegeneration in the MPTP model of Parkinson's disease | PNAS
To adequately quantify TH-positive neurons, we used the nuclear counterstain methyl green (Vector Laboratories) and the ... 4 A and B), but does so quite effectively in the presence of glia (Fig. 4 C and D), we argue that the neurotoxicity of MPTP/MPP ... 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine;. MPP+,. 1-methyl-4-phenylpyridinium;. SNpc,. substantia nigra pars compacta;. CGN ... 3,4-dihydroxyphenylacetic acid;. HVA,. homovanilic acid;. MAPK,. mitogenactivated protein kinase;. TH,. tyrosine hydroxylase;. ...
more infohttp://www.pnas.org/content/98/25/14669
User:Kipmaster/english-index - Wiktionary  User:Kipmaster/english-index - Wiktionary
Text is available under the Creative Commons Attribution-ShareAlike License; additional terms may apply. By using this site, you agree to the Terms of Use and Privacy Policy. ...
more infohttps://en.wiktionary.org/wiki/User:Kipmaster/english-index
Role of Prostaglandins in Neuroinflammatory and Neurodegenerative Diseases  Role of Prostaglandins in Neuroinflammatory and Neurodegenerative Diseases
20-tetranorisocarbacyclin methyl ester, a selective central type PGI2 receptor ligand, reduced brain damage induced by middle ... The KO animals were also less sensitive to excitotoxicity induced by unilateral intrastriatal N-methyl-D-aspartate injection. ... 3.5.2. PGE2, PGF2α, and PGA1. Administration of 3-NP enhances PGE2 and PGF2α in the striatum [154, 155]. These prostaglandins ... 3.3.1. PLA2 and COX. It has been shown that mice carrying a mutation of the cPLA2 gene, leading to an absence of cPLA2 activity ...
more infohttps://www.hindawi.com/journals/mi/2012/946813/
Drug Development and Drug Interactions:  Table of Substrates, Inhibitors and Inducers  Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers
1-888-INFO-FDA (1-888-463-6332). Contact FDA Subscribe to FDA RSS feeds Follow FDA on Twitter Follow FDA on Facebook View FDA ... OAT1/OAT3: (1) AUC fold-increase ≥1.5 for at least one of clinical substrates in Table 2-3 with co-administration and (2) in ... P-gp: (1) AUC fold-increase≥2 with verapamil or quinidine co-administration and (2) in vitro transport by P-gp expression ... OATP1B1/OATP1B3: (1) AUC fold-increase ≥2 for at least one of clinical substrates in Table 2-3 with co-administration and (2) ...
more infohttps://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm093664.htm
Plus it  Plus it
... methyl-d-aspartate receptors. These results suggest that DM may be a promising therapeutic agent for the treatment of ... methyl-d-aspartate antagonist dizocilpine maleate failed to afford significant neuroprotection, it is unlikely that the ... 1-methyl-4-phenylpyridinium. DA. dopamine. TH. tyrosine hydroxylase. ir. immunoreactive. SOD. superoxide dismutase. HBSS. Hanks ... Pay Per Article - You may access this article (from the computer you are currently using) for 1 day for US$35.00 ...
more infohttp://jpet.aspetjournals.org/content/305/1/212
Cannabinoid Receptor Type 1 Protects Nigrostriatal Dopaminergic Neurons against MPTP Neurotoxicity by Inhibiting Microglial...  Cannabinoid Receptor Type 1 Protects Nigrostriatal Dopaminergic Neurons against MPTP Neurotoxicity by Inhibiting Microglial...
CB1. cannabinoid receptor type 1. CB2. cannabinoid receptor type 2. Ct. threshold cycle. DA. dopaminergic. DIV. days in vitro. ... SN tissues were prepared for MAC-1 (A, D, G, J, M, P) and ED-1 (B, E, H, K, N, Q) immunostaining to detect microglia or for ... 1A-L, 2A-F). TH immunostaining revealed that four injections of MPTP led to damage in SN (Fig. 1C, 1D) and STR (Fig. 2B) ... 4A, 4B; p , 0.01) and Rac-1 (Fig. 4A, 4B; p , 0.01) were dramatically decreased in SN treated with WIN55,212-2. This effect was ...
more infohttp://www.jimmunol.org/content/187/12/6508.full
JCI -
D-β-Hydroxybutyrate rescues mitochondrial respiration and mitigates features of Parkinson disease  JCI - D-β-Hydroxybutyrate rescues mitochondrial respiration and mitigates features of Parkinson disease
Transgenic mice with increased Cu/Zn-superoxide dismutase activity are resistant to N-methyl-4-phenyl-1,2,3,6- ... Energy-dependent uptake of N-methyl-4-phenylpyridinium, the neurotoxic metabolite of 1-methyl-4-phenyl-1,2,3,6- ... Parkinsonism-inducing neurotoxin, N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine: uptake of the metabolite N-methyl-4- ... phenylpyridinium by dopamine neurons explains selective toxicity. Proc. Natl. Acad. Sci. U. S. A. 1985. 82:2173-2177. View this ...
more infohttps://www.jci.org/articles/view/18797
Plus it  Plus it
1 (WinNonlin 5.0.1; Pharsight Inc., Mountain View, CA):. (1)where v0 is the net uptake without inhibitor, I is the inhibitor ... 4. Effects of vandetanib and PYR on the uptake of MPP+ and metformin by MATE2K-HEK cells. Time-dependent uptake of 1 µM [3H]MPP ... 1 (B and E), vandetanib (0.08-100 µM) did not inhibit human OAT1-mediated [3H]PAH uptake (Fig. 1B) or OAT3-mediated [3H]E3S ... 1-methyl-4-phenylpyridinium. NSCLC. non-small cell lung cancer. OAT. organic anion transporter. OCT. organic cation transporter ...
more infohttp://dmd.aspetjournals.org/content/41/12/2095
Plus it  Plus it
1A and B) demonstrated that MDCKII-OCT1 cells were able to mediate uptake of MPP+ (50 μmol/l) into cells with an uptake ratio ... 1C).. Inhibition of OATPs and OCT1 by antidiabetic drugs.. The results of the inhibition experiments are summarized in Table 1 ... 2-4. Metformin did not inhibit OATP1B1-, OATP1B3-, or OATP2B1-mediated BSP uptake (Fig. 2) or uptake of the OCT1 substrate MPP+ ... 4. Inhibition of MPP+ and metformin uptake by oral antidiabetic drugs in MCDKII-OCT1 cells. A: Inhibitory effect of repaglinide ...
more infohttp://diabetes.diabetesjournals.org/content/57/6/1463
Plus it  Plus it
Methyl-3H]MPP+ was from Perkin-Elmer (Boston, MA), and TEA bromide [ethyl-1-14C] was from American Radiolabeled Chemicals (St. ... MDCK cells were incubated with oxaliplatin (20 μmol/L) or [Pt(R,R-DACH)(H2O)2]2+ (1 μmol/L) in PB-Cl or PB-SO4 buffer at 37°C ... 4B) and was markedly reduced by cimetidine (0.00216 ± 0.00031 pmol/μg DNA, rb = 9.37 ± 0.66 × 10−6 versus 7.13 ± 1.02 × 10−7). ... Preparation of [Pt(NH3)2(trans-1,2-(OCO)2C6H10)]. The compound was prepared as described for the Pt-DACH derivative ( 37). ...
more infohttp://cancerres.aacrjournals.org/content/66/17/8847
A model of MPP+ induced generation of two waves of ROS  | Open-i  A model of MPP+ induced generation of two waves of ROS | Open-i
A two-wave ROS cascade was identified: 1) as a first wave, mitochondrial H2O2 production was first noted at three hours of MPP+ ... A two-wave ROS cascade was identified: 1) as a first wave, mitochondrial H2O2 production was first noted at three hours of MPP+ ... Generation of reactive oxygen species in 1-methyl-4-phenylpyridinium (MPP+) treated dopaminergic neurons occurs as an NADPH ... Generation of reactive oxygen species in 1-methyl-4-phenylpyridinium (MPP+) treated dopaminergic neurons occurs as an NADPH ...
more infohttps://openi.nlm.nih.gov/detailedresult.php?img=PMC3198931_1742-2094-8-129-9&req=4
  • Here we measured binding and transport of model substrate 1-methyl-4-phenylpyridinium + (MPP + ) by cell-free-expressed fusion proteins of rOCT1 and various rOCT1 mutants with green fluorescent protein that were reconstituted into nanodiscs or proteoliposomes. (aspetjournals.org)
  • This study shows that the human organic cation transporters (OCT) 1 and 2 ( SLC22A1 and SLC22A2 ) markedly increase oxaliplatin, but not cisplatin or carboplatin, accumulation and cytotoxicity in transfected cells, indicating that oxaliplatin is an excellent substrate of these transporters. (aacrjournals.org)
  • The assay has been used routinely in our laboratory for the measurement of MPP+ levels in brain tissue from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice, and can be used to distinguish neuroprotective efficacy and monoamine oxidase inhibition. (mdx.ac.uk)
  • The observed neuroprotection and inhibition of microglial activation were reversed upon treatment with CB 1 receptor selective antagonists AM251 and/or SR14,716A, confirming the involvement of the CB 1 receptor. (jimmunol.org)
  • Although no inhibition of OAT1 and OAT3 was observed, inhibition of OCT2-mediated uptake of 1-methyl-4-phenylpyridinium (MPP + ) and metformin was evident (IC 50 of 73.4 ± 14.8 and 8.8 ± 1.9 µ M, respectively). (aspetjournals.org)
  • Vandetanib was evaluated as an inhibitor of human organic anion transporter 1 (OAT1), OAT3, organic cation transporter 2 (OCT2), and multidrug and toxin extrusion (MATE1 and MATE2K) transfected (individually) into human embryonic kidney 293 cells (HEK293). (aspetjournals.org)
  • These peripheral-derived factors and intrinsically generated cytokines/chemokines, α-synuclein, corticotropin-releasing hormone (CRH), substance P (SP), beta amyloid 1-42 (Aβ1-42) peptide and amyloid precursor proteins can activate glial cells, T-cells and mast cells in the brain can induce additional release of inflammatory and neurotoxic molecules contributing to chronic neuroinflammation and neuronal death. (frontiersin.org)
  • The most prominent biochemical changes in PD involve reduction of the striatal dopamine levels that may result in abnormal motor behavior, including resting tremor, rigidity, and bradykinesia ( 1 , 2 ). (jimmunol.org)
  • In addition, because LPS did not produce any significant increase in the release of excitatory amino acids from neuron-glia cultures and N- methyl- d -aspartate antagonist dizocilpine maleate failed to afford significant neuroprotection, it is unlikely that the neuroprotective effect of DM is mediated through N- methyl- d -aspartate receptors. (aspetjournals.org)
  • The neuroprotective effect of minocycline is associated with marked reductions in inducible NO synthase (iNOS) and caspase 1 expression. (pnas.org)
  • These results indicated that DJ-1 was an upstream regulator of Nrf2 in the neuroprotective effects of Sal. (hindawi.com)
  • Cells were treated with MPP+ (MPTP metabolite) following siRNA silencing of the Nox2-stabilizing subunit p22phox, or simultaneously with NADPH oxidase pharmacological inhibitors or with losartan to antagonize angiotensin II type 1 receptor-induced NADPH oxidase activation. (nih.gov)
  • Obata [1] examined the antioxidant effect of phytic acid on iron (II)-enhanced hydroxyl radical (*OH) generation induced by MPP+ in the extracellular fluid of rat striatum. (wikiversity.org)
  • It is now well established that drug transporters are major determinants of drug disposition and effects ( 1 , 2 ). (diabetesjournals.org)
  • mPGES-1 is an inducible enzyme and is expressed also in activated microglia [ 15 , 16 ]. (hindawi.com)
  • B2 contained 41% of the actin, 100% of the tubulin, and most of the flotillin-1 and caveolin in myelin, whereas B1 contained more NCAM120 and other proteins than B2. (wiley.com)
  • But Nrf2 silence did not significantly impact Sal-exhibited effects on DJ-1 expression. (hindawi.com)
  • Sal significantly prevented MPP+-induced decrease of the mRNA and protein expression of DJ-1 in SH-SY5Y cells. (hindawi.com)
  • Moreover, silencing of DJ-1 significantly inhibited Sal-induced increase in mRNA and protein expression of Nrf2, GCLc, SOD1, and SOD2 in MPP+-treated SH-SY5Y cells. (hindawi.com)
  • A high-throughput liquid chromatography/tandem mass spectrometry method has been developed for the quantitative assessment of 1-methyl-4-phenylpyridinium (MPP+) in brain tissue samples. (mdx.ac.uk)
  • Kanthasamy, A. G. and Reddy, M. B. ( 2008 ) Abstract Toxicology 245 (1-2):101 - 108. (wikiversity.org)
  • Positive control inducers were 50 µM Omeprazole for CYP1A2, 1 mM Phenobarbital for CYP2B6, and 10 µM Rifampicin for CYP3A4. (corning.com)