1 methyl 4 phenylpyridinium. Medical search

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.

A dopaminergic neurotoxic compound which produces irreversible clinical, chemical, and pathological alterations that mimic those found in Parkinson disease.

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)

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.

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.

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.

A botanical insecticide that is an inhibitor of mitochondrial electron transport.

Pesticides used to destroy unwanted vegetation, especially various types of weeds, grasses (POACEAE), and woody plants. Some plants develop HERBICIDE RESISTANCE.

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.

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.

Any drugs that are used for their effects on dopamine receptors, on the life cycle of dopamine, or on the survival of dopaminergic neurons.

A class of sodium-independent nucleoside transporters that mediate the facilitative transport of NUCLEOSIDES.

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.

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)

Neurons whose primary neurotransmitter is DOPAMINE.

A family of vesicular amine transporter proteins that catalyze the transport and storage of CATECHOLAMINES and indolamines into SECRETORY VESICLES.

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.

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.

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.

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.

A deaminated metabolite of LEVODOPA.

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 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.

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.

Positively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis.

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.

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.

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.

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.

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.

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.

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.

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.

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)

The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.

A non-selective inhibitor of nitric oxide synthase. It has been used experimentally to induce hypertension.

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.

The inner portion of the adrenal gland. Derived from ECTODERM, adrenal medulla consists mainly of CHROMAFFIN CELLS that produces and stores a number of NEUROTRANSMITTERS, mainly adrenaline (EPINEPHRINE) and NOREPINEPHRINE. The activity of the adrenal medulla is regulated by the SYMPATHETIC NERVOUS SYSTEM.

Organelles in CHROMAFFIN CELLS located in the adrenal glands and various other organs. These granules are the site of the synthesis, storage, metabolism, and secretion of EPINEPHRINE and NOREPINEPHRINE.

Cells that store epinephrine secretory vesicles. During times of stress, the nervous system signals the vesicles to secrete their hormonal content. Their name derives from their ability to stain a brownish color with chromic salts. Characteristically, they are located in the adrenal medulla and paraganglia (PARAGANGLIA, CHROMAFFIN) of the sympathetic nervous system.

The cells of the body which stain with chromium salts. They occur along the sympathetic nerves, in the adrenal gland, and in various other organs.

A general class of ortho-dihydroxyphenylalkylamines derived from tyrosine.

A glycoside obtained from Digitalis purpurea; the aglycone is digitogenin which is bound to five sugars. Digitonin solubilizes lipids, especially in membranes and is used as a tool in cellular biochemistry, and reagent for precipitating cholesterol. It has no cardiac effects.

The part of brain that lies behind the BRAIN STEM in the posterior base of skull (CRANIAL FOSSA, POSTERIOR). It is also known as the "little brain" with convolutions similar to those of CEREBRAL CORTEX, inner white matter, and deep cerebellar nuclei. Its function is to coordinate voluntary movements, maintain balance, and learn motor skills.

Guanosine cyclic 3',5'-(hydrogen phosphate). A guanine nucleotide containing one phosphate group which is esterified to the sugar moiety in both the 3'- and 5'-positions. It is a cellular regulatory agent and has been described as a second messenger. Its levels increase in response to a variety of hormones, including acetylcholine, insulin, and oxytocin and it has been found to activate specific protein kinases. (From Merck Index, 11th ed)

A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.

Freedom of equipment from actual or potential hazards.

Process that is gone through in order for a device to receive approval by a government regulatory agency. This includes any required preclinical or clinical testing, review, submission, and evaluation of the applications and test results, and post-marketing surveillance. It is not restricted to FDA.

An agency of the PUBLIC HEALTH SERVICE concerned with the overall planning, promoting, and administering of programs pertaining to maintaining standards of quality of foods, drugs, therapeutic devices, etc.

The relative equivalency in the efficacy of different modes of treatment of a disease, most often used to compare the efficacy of different pharmaceuticals to treat a given disease.

The transference of a kidney from one human or animal to another.

The release of stem cells from the bone marrow into the peripheral blood circulation for the purpose of leukapheresis, prior to stem cell transplantation. Hematopoietic growth factors or chemotherapeutic agents often are used to stimulate the mobilization.

A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.

Poly(ADP-ribose) polymerase activation mediates 1-methyl-4-phenyl-1, 2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism. (1/255)

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)

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

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)

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

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)

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

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)

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

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)

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

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)

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

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)

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

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)

The industrial synthesis of MPP+ for sale as the herbicide cyperquat used methyl chloride as the source of the methyl group. ... MPP+ (1-methyl-4-phenylpyridinium) is a positively charged organic molecule with the chemical formula C12H12N+. It is a ... Zhang Y, Zhou TY, Zhang KD, Dai JL, Zhu YY, Zhao X (June 2014). "Encapsulation enhanced dimerization of a series of 4-aryl-N- ... 18 (4): 409-14. doi:10.1089/jmf.2014.3241. PMID 25325362. Hassan MN, Thakar JN, Grimes JD (1987). "Cyperquat (MPP+), but not ...

https://en.wikipedia.org/wiki/MPP

doi:10.1385/1-59259-365-8:133 Lannuzel, A. and Michel, P. P. (2008). Atypical Parkinsonism in the French West Indies: The Plant ... 63 (4): 1053-1056. doi:10.1021/jf504500g. PMID 25594104. Potts, L. F.; Luzzio, F. A.; Smith, S. C.; Hetman, M; Champy, P; ... 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 ... Cortico-Subcortical Dynamics in Parkinson¿s Disease, 1-8. doi:10.1007/978-1-60327-252-0_18 Caparros-Lefebvre, D., & Elbaz, A. ( ...

https://en.wikipedia.org/wiki/Annonacin

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 (2005 ...

https://en.wikipedia.org/wiki/Phosphoenolpyruvate_carboxykinase

Retrieved 4 November 2013. Kleiman, Mark A.R.; Hawdon, James E. (2011). Encyclopedia of drug policy. Thousand Oaks: Sage ... 1-Methyl-4-phenylpyridinium (MPP+), a metabolite of MPTP, causes rapid onset of irreversible symptoms similar to Parkinson's ... ISBN 978-92-1-148277-5. Retrieved 9 January 2017. The National Drug Control Strategy: 2000 Annual Report. Washington, D.C.: ... 1 (4): 36-39. Retrieved 23 March 2018. "Club Drugs". National Institute on Drug Abuse. Retrieved 9 January 2017. "DEPARTMENT OF ...

https://en.wikipedia.org/wiki/Clandestine_chemistry

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 ... 107 (4): 481-5. doi:10.7326/0003-4819-107-4-481. PMID 3631786. Ricaurte GA, Forno LS, Wilson MA, DeLanney LE, Irwin I, Molliver ... 7 (1): 2-13. doi:10.1002/mds.870070103. PMID 1557062. S2CID 31485426. Widner H, Tetrud J, Rehncrona S, Snow B, Brundin P, ...

https://en.wikipedia.org/wiki/William_Langston

Structural analogs of desmethylprodine with different N-substituents than a methyl group on the piperidine have been ... 13 (4): 367-74. doi:10.1016/0376-8716(84)90004-8. PMID 6148225. Davis GC, Williams AC, Markey SP, Ebert MH, Caine ED, Reichert ... 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- ...

https://en.wikipedia.org/wiki/Desmethylprodine

In all known secalonic acids, the methyl and methoxycarbonyl substituents are found to be trans to each other, and X-ray ... 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, ... The 2-2'linked secalonic acid A isomerizes in DMSO at room temperature to the 2-4'linked secalonic acid A and 4-4'linked ...

https://en.wikipedia.org/wiki/Secalonic_acid

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 ...

https://en.wikipedia.org/wiki/Competitive_inhibition

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 the neurotoxin 1-methyl-4-phenylpyridinium (MPP) via the OCT3 transporter in ... 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) fluorescence through ...

https://en.wikipedia.org/wiki/Decynium-22

... (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. PMID 298352. "Success reported using fetal tissue to repair a brain". The New ... 2 (1): 141-151. doi:10.1038/nprot.2006.342. PMID 17401348. "Pesticides and Parkinson's Disease - A Critical Review" (PDF). ... 1. Mitteilung". Helvetica Chimica Acta. 35 (5): 1527-1536. doi:10.1002/hlca.19520350514. "1-Methyl-4-phenyl-1,2,3,6- ...

https://en.wikipedia.org/wiki/MPTP

Table 1 represents a summary of the PD animal models and details regarding their mechanisms of action, pathogenesis, and ... ISBN 978-1-259-64115-2. Hatcher, Jaime M.; Pennell, Kurt D.; Miller, Gary W. (June 2008). "Parkinson's disease and pesticides: ... Braak staging is a widely used method to measure the stage of pathology (stage 1 being the lowest level of pathology and stage ... Protein Deglycase (DJ-1) mutations are associated with recessive forms of familial parkinsonism. It is a molecular chaperone ...

https://en.wikipedia.org/wiki/Animal_models_of_Parkinson's_disease

... methyl ester MeSH D03.383.725.210 - dimethindene MeSH D03.383.725.220 - 2,2'-dipyridyl MeSH D03.383.725.227 - disopyramide MeSH ... methyl ester MeSH D03.383.725.547.950 - xanthinol niacinate MeSH D03.383.725.565 - nicotinyl alcohol MeSH D03.383.725.592 - ... 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 - ...

https://en.wikipedia.org/wiki/List_of_MeSH_codes_(D03)

27 (4): 1064-74. doi:10.1002/hep.510270423. PMID 9537447. S2CID 11899686. Yang H, Zhou L, Shi Q, Zhao Y, Lin H, Zhang M, Zhao S ... 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 ...

https://en.wikipedia.org/wiki/GOT2

Phenylethylamine (10), amphetamine [AMPH (11 & 12)], methylenedioxy methamphetamine [METH (13)] and N-methyl-4-phenylpyridinium ... 16 (1): 9-18. doi:10.1016/0031-9422(77)83004-5. Lynnes T, Horne SM, Prüß BM (2014). "ß-Phenylethylamine as a novel nutrient ... 96 (1): 165-71. doi:10.1016/j.meatsci.2013.06.030. PMID 23896151. Acetoacetic acid (AAA) and ß-phenylethylamine (PEA) performed ... 2 (1): 3-19. CiteSeerX 10.1.1.329.563. doi:10.2174/157488707779318107. PMID 18473983. It has also been suggested that the ...

https://en.wikipedia.org/wiki/Phenethylamine

Annona crassiflora Mart.[1]. Guanabanus muricatus M.Gómez. Guanabanus muricatus (L.) M.Gómez[2]. Annona bonplandiana Kunth. ... 1. Retrieved 2008-04-18.. *. UBC Botanical Garden and Centre for Plant Research (2007-04-13). "Annona muricata". Botany Photo ... 1 February 2017. Retrieved 25 May 2018.. *^ Matsushige, A; Kotake, Y; Matsunami, K; Otsuka, H; Ohta, S; Takeda, Y (2012). " ... Annona muricata is a small, upright, evergreen tree that can grow to about 30 feet (9.1 m) tall.[4][5][8][9] ...

https://en.wikipedia.org/wiki/Guanabana

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 ...

https://en.wikipedia.org/wiki/Vesicular_monoamine_transporter

Phenylethylamine (10), amphetamine [AMPH (11 & 12)], methylenedioxy methamphetamine [METH (13)] and N-methyl-4-phenylpyridinium ... Primarily: MAO-B[3][4][5]. Other enzymes: MAO-A,[5][6] SSAOs (AOC2 & AOC3),[5][7] PNMT,[3][4][5] AANAT,[5] FMO3,[8][9] and ... Primarily: MAO-B[3][4][5]. Other enzymes: MAO-A,[5][6] SSAOs (AOC2 & AOC3),[5][7] PNMT,[3][4][5] AANAT,[5] FMO3,[8][9] and ... 16 (1): 9-18. doi:10.1016/0031-9422(77)83004-5.. *^ a b c d e Irsfeld M, Spadafore M, Prüß BM; Spadafore; Prüß (September 2013 ...

https://en.m.wikipedia.org/wiki/Phenethylamine

Kalgutkar AS, Nguyen HT (September 2004). "Identification of an N-methyl-4-phenylpyridinium-like metabolite of the ... Guarino, Ben (4 May 2016). "Abuse of diarrhea medicine you know well is alarming physicians". Washington Post. Retrieved 6 May ... 69 (1): 83-86. doi:10.1016/j.annemergmed.2016.03.047. PMID 27140747. Mukarram O, Hindi Y, Catalasan G, Ward J (2016). " ... ISBN 978-92-1-130230-1. Archived from the original on 8 September 2017. US patent 5612054, Jeffrey L. Garwin, "Pharmaceutical ...

https://en.wikipedia.org/wiki/Loperamide

The subcellular localization of the incorporated [methyl-3H]MPP+ was examined by differential centrifugation and sucrose ... As an extension of this hypothesis, the relative resistance of some brain monoaminergic neurons to the toxic actions of 1- ... methyl-4-phenyl-1,2,3,6-tetrahydropyridine may result from the subcellular sequestration of MPP+ in the storage vesicle. ... Subcellular compartmentalization of 1-methyl-4-phenylpyridinium with catecholamines in adrenal medullary chromaffin vesicles ...

https://www.pnas.org/content/84/22/8160?ijkey=5fe895003d5c71ecfc2b558a1674eea37800a4e9&keytype2=tf_ipsecsha

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.. ...

https://www.ncbi.nlm.nih.gov/pubmed/21615675

2006 Feb 1;83(2):233-42. doi: 10.1002/jnr.20696. Authors Martine Barkats 1 , Philippe Horellou, Philippe Colin, Stéphanie ... 1-methyl-4-phenylpyridinium neurotoxicity is attenuated by adenoviral gene transfer of human Cu/Zn superoxide dismutase J ... 1 Laboratoire de Genetique Moleculaire de la Neurotransmission et des Processus Neurodegeneratifs (LGN), CNRS UMR 7091, Paris, ... before exposure to 1 mM of the 1-methyl-4-phenylpyridinium ion (MPP+). A strong neuroprotective effect of SOD1 gene transfer ...

https://pubmed.ncbi.nlm.nih.gov/16353238/?dopt=Abstract

Cellular cholesterol content, assessed by thin layer chromatography, was manipulated using empty methyl-β-cyclodextrin (mβcd) ... Transport activity of OCT2 was measured using [3H]1-methyl-4-phenylpyridinium (MPP+). A 20-minute incubation with mβcd reduced ... Pay Per Article - You may access this article (from the computer you are currently using) for 1 day for US$35.00 ... Plasma Membrane Cholesterol Regulates the Allosteric Binding of 1-Methyl-4-Phenylpyridinium to Organic Cation Transporter 2 ( ...

http://jpet.aspetjournals.org/content/372/1/46

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 ...

http://jpet.aspetjournals.org/content/262/1/225

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 ...

http://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. 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 ...

http://molpharm.aspetjournals.org/content/95/2/169/tab-e-letters

... 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 ...

https://www.semanticscholar.org/paper/Glia-Maturation-Factor-Deficiency-Suppresses-Stress-Khan-Kempuraj/b337c34eefbc67054b7d95d3ed6a41711196b2ed

... 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 ...

https://www.semanticscholar.org/paper/Formation-of-superoxide-and-hydroxyl-radicals-from-Sinha-Singh/c33b41cbf1fd42654141a4ece7d704ee07969283

Cultured PC12 cells were either treated with MPP+ alone or co-treated with one of the omega-6 fatty acids for 1 day. Cell ... In the current study, the potential of two omega-6 fatty acids (i.e. arachidonic acid and linoleic acid) in alleviating 1- ... methyl-4-phenylpyridinium (MPP+)-induced cytotoxicity in PC12 cells was examined. ... viability was then assessed by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cells ...

https://lipidworld.biomedcentral.com/articles/10.1186/1476-511X-13-197

Y1 - 2018/1/15. N2 - To investigate the role of nitric oxide (NO)/reactive oxygen species (ROS) redox signaling in Parkinsons ... Involvement of nitric oxide/reactive oxygen species signaling via 8-nitro-cGMP formation in 1-methyl-4-phenylpyridinium ion- ... Involvement of nitric oxide/reactive oxygen species signaling via 8-nitro-cGMP formation in 1-methyl-4-phenylpyridinium ion- ... Involvement of nitric oxide/reactive oxygen species signaling via 8-nitro-cGMP formation in 1-methyl-4-phenylpyridinium ion- ...

https://kyushu-u.pure.elsevier.com/en/publications/involvement-of-nitric-oxidereactive-oxygen-species-signaling-via-

英文关键词: minocycline PC12 cell apoptosis parkinson disease 1-methyl-4-mhenylpyridinium. ... Minocycline protects the apoptosis of PC12 cells induced by 1-methyl-4-phenylpyridinium. ...

http://jnmu.njmu.edu.cn/zr/ch/reader/view_abstract.aspx?file_no=jnmu050506&flag=1

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;. ...

http://www.pnas.org/content/98/25/14669

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. ...

https://en.wiktionary.org/wiki/User:Kipmaster/english-index

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 ...

http://www.jimmunol.org/content/187/12/6508.full

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) ...

https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm093664.htm

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 ...

https://www.hindawi.com/journals/mi/2012/946813/

2008 Mar 12;245(1-2):101-8. doi: 10.1016/j.tox.2007.12.017. Epub 2007 Dec 27. ... 1 Department of Biomedical Sciences, Iowa State University, Ames, IA, United States. ... on 1-methyl-4-phenylpyridinium (MPP(+))-induced cell death in immortalized rat mesencephalic/dopaminergic cells. Cell death was ...

https://pubmed.ncbi.nlm.nih.gov/18255213/

Overexpression of annexin A1 suppresses pro-inflammatory factors in PC12 cells induced by 1-methyl-4-phenylpyridinium ... production and suppressing pro-inflammatory responses in PC12 cells induced by 1-methyl-4-phenylpyridinium [MPP+] ...

https://search.bvsalud.org/gim/resource/en/emr-183009

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 ( ...

http://eprints.mdx.ac.uk/22824/

... and l-methyl-4-(4- nitrophenyl) pyridinium (analog 1), on the energy metabolism in pheochromocytoma PC12 cells. MPP+ inhibited ... and l-methyl-4-(4- nitrophenyl) pyridinium (analog 1), on the energy metabolism in pheochromocytoma PC12 cells. MPP+ inhibited ... and l-methyl-4-(4- nitrophenyl) pyridinium (analog 1), on the energy metabolism in pheochromocytoma PC12 cells. MPP+ inhibited ... and l-methyl-4-(4- nitrophenyl) pyridinium (analog 1), on the energy metabolism in pheochromocytoma PC12 cells. MPP+ inhibited ...

https://kyushu-u.pure.elsevier.com/en/publications/changes-of-energy-metabolism-induced-by-1-methyl-4-phenylpyridini

Neuronal accumulation of 1-methyl-4-phenylpyridinium ion (MPP+), the metabolite of neural toxin, 1-methyl-4-phenyl-1,2,3,6- ... Inhibition of platelet aggregation by 1-methyl-4-phenyl pyridinium ion (MPP plus ) through ATP depletion: Evidence for the ... Inhibition of platelet aggregation by 1-methyl-4-phenyl pyridinium ion (MPP plus ) through ATP depletion: Evidence for the ...

https://repository.hanyang.ac.kr/handle/20.500.11754/74989

Y1 - 2008/6/1. N2 - In the present study we provide evidence for hydroxyl radical ( •OH) scavenging action of nitric oxide (NO ... Solutions of NG, SNAP and SIN-1, exposed to air for 48 h to remove NO•, when administered similarly failed to attenuate MPP+- ... While NG, SNAP and SIN-1 attenuated MPP+-induced •OH generation in the mitochondria, and in a Fenton-like reaction, SNP caused ... Solutions of NG, SNAP and SIN-1, exposed to air for 48 h to remove NO•, when administered similarly failed to attenuate MPP+- ...

https://augusta.pure.elsevier.com/en/publications/evidence-for-hydroxyl-radical-scavenging-action-of-nitric-oxide-d

METHODS After being pretreated with DMY 5, 10, 20, 40 and 80 μmol · L-1 for 0.5 h, PC12 cells were incubated with DMEM culture ... OBJECTIVE To observe the effect of dihydromyricetin (DMY) on cell injury induced by 1-methyl-4-phenylpyridinium (MPP+) in PC12 ... Expressions of autophagy related protein, Beclin-1, microtubule-associated protein light chain 3 (LC3) and p62 were measured by ... Dihydromyricetin inhibits PC12 cell injury induced by 1-methyl-4-phenylpyridinium by up-regulating autophagy activity / 中国药理学与毒 ...

https://search.bvsalud.org/gim/resource/en/wpr-705200

Theoretical-Studies On Mechanism Of Mptp Action - Et Interference By Mpp+ (1-Methyl-4-Phenylpyridinium) With Mitochondrial ...

https://vivo.nkn.uidaho.edu/vivo/display/WA1991EV83100004

Transgenic mice with increased Cu/Zn-superoxide dismutase activity are resistant to N-methyl-4-phenyl-1,2,3,6- ... Figure 1. Fatty acid-induced uncoupling in UCP2 WT/TG and WT/KO mice and UCP expressions. A, Exposure to the free fatty acid ... Scale bar: (in B) A, B, 1 μm. C, Quantification of the number of mitochondria in UCP2 WT/TG and UCP2 WT/KO mice. Data are ... 1B); UCP4 mRNA was more robustly expressed than BMCP1. The levels of these transcripts did not differ between the various ...

http://www.jneurosci.org/content/25/1/184

Rat primary neuron-astroglia cocultures were obtained by suppressing microglial proliferation with 1.5 mM L-leucine methyl ... 1⇓A). Consistent with a previous report, TGF-β1 alone at 3 ng/ml show a slight but significant neurotrophic effect as measured ... Two and 4 days after MPP+ treatment, TGF-β1 was added again to the TGF-β1-treated cultures. On day 4, the release of superoxide ... FIGURE 4. Microglia PHOX is the target of TGF-β1 inhibition in LPS-induced neurotoxicity. PHOX+/+ and PHOX−/− mice neuron-glia ...

https://www.jimmunol.org/content/181/1/660

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 ...

https://www.jci.org/articles/view/18797

Position: hg38 chr11:14,279,337-14,294,827 Size: 15,491 Coding Exon Count: 4 Page Index. Sequence and Links. UniProtKB Comments ... Diseases sorted by gene-association score: ovarian cancer, somatic* (112), teratocarcinoma (4), breast cancer (2). * = Manually ... uc057zhr.1. UCSC ID: ENST00000534746.5. RefSeq Accession: NM_001177314. Protein: P62070 (aka RRAS2_HUMAN or RRA2_HUMAN). CCDS: ... Pseudogenes of this gene are found on chromosomes 1 and 2. Alternate splicing results in multiple transcript variants. [ ...

https://genome.ucsc.edu/cgi-bin/hgGene?hgg_gene=ENST00000534746.5&hgg_chrom=chr11&hgg_start=14278938&hgg_end=14354500&hgg_type=knownGene&db=hg38

N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide. PUFAs. polyunsaturated fatty acids ... NCEH-1. knockdown increases the aggregation of α-Syn and dopamine neural damage in C. elegans. , while inhibition of ACAT gave ... Figure 1.. Summary of signaling pathways involved in α-Syn aggregation and potential connection of 18-kDa translocator protein ... 1. Synucleins family-new insights and prospects. Synucleins are a family of small and soluble proteins expressed mostly in ...

https://www.intechopen.com/books/synucleins-biochemistry-and-role-in-diseases/alpha-synuclein-aggregation-cholesterol-transport-and-the-18-kda-translocator-protein

As an extension of this hypothesis, the relative resistance of some brain monoaminergic neurons to the toxic actions of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine may result from the subcellular sequestration of MPP+ in the storage vesicle. (pnas.org)
DLP1-dependent mitochondrial fragmentation mediates 1-methyl-4-phenylpyridinium toxicity in neurons: implications for Parkinson's disease. (nih.gov)
These cells are popular because they are able to synthesize and release catecholamines in a similar manner as dopaminergic neurons and adrenal medullary chromaffin cells [ 4 ]. (biomedcentral.com)
In vitro studies using primary cultures of mesencephalic and cerebellar granule neurons (CGN) and/or glia demonstrate that minocycline inhibits both 1-methyl-4-phenylpyridinium (MPP + )-mediated iNOS expression and NO-induced neurotoxicity, but MPP + -induced neurotoxicity is inhibited only in the presence of glia. (pnas.org)
MPTP selectively destroys dopamine neurons in the substantia nigra, resulting in a Parkinson's-like syndrome in many species, including humans, monkeys, and mice ( 4 , 5 ). (pnas.org)
This study examined whether the cannabinoid receptor type 1 (CB 1 ) receptor contributes to the survival of nigrostriatal dopaminergic (DA) neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. (jimmunol.org)
MPTP induced significant loss of nigrostriatal DA neurons and microglial activation in the substantia nigra (SN), visualized with tyrosine hydroxylase or macrophage Ag complex-1 immunohistochemistry. (jimmunol.org)
Interestingly, cannabinoids protected DA neurons against 1-methyl-4-phenyl-pyridinium neurotoxicity in cocultures of mesencephalic neurons and microglia, but not in neuron-enriched mesencephalic cultures devoid of microglia. (jimmunol.org)
Because excessive iron can induce oxidative stress subsequently causing degradation of nigral dopaminergic neurons in PD, we determined the protective effect of a naturally occurring iron chelator, phytic acid (IP6), on 1-methyl-4-phenylpyridinium (MPP(+))-induced cell death in immortalized rat mesencephalic/dopaminergic cells. (nih.gov)
Lack of UCP2 increased the sensitivity of dopamine neurons to 1-methyl-4-phenyl-1,2,5,6 tetrahydropyridine (MPTP), whereas UCP2 overexpression decreased MPTP-induced nigral dopamine cell loss. (jneurosci.org)
PD is attributed to loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) and characterized by the presence of ubiquitinated alpha-synuclein- ( α -syn-) containing cytoplasmic inclusions called Lewy bodies in surviving SNpc neurons [ 3 , 4 ]. (hindawi.com)
Generation of reactive oxygen species in 1-methyl-4-phenylpyridinium (MPP+) treated dopaminergic neurons occurs as an NADPH oxidase-dependent two-wave cascade. (nih.gov)
The death of DA neurons in SNc could further inhibit thalamic activity, and reduce the excitatory input to the motor cortex, resulting in slow movements and limbs stiff in PD patients [ 4 ]. (mdpi.com)
TRPM7, which is ubiquitously expressed and shown to facilitate cholinergic vesicle fusion with plasma membrane in neurons ( 4 ), also plays a role in detoxification of intermediates of melanin synthesis. (physiology.org)
Recently, bee venom was reported to protect dopaminergic neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine induced mice PD model, however, the underlying mechanism is not fully understood. (blogspot.com)

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin that causes dopaminergic neurodegeneration and a mitochondrial deficit reminiscent of PD. (jci.org)
Journal Article] Detection of a novel neurotoxic metabolite of Parkinson's disease-related neurotoxin, 1-benzyl-1,2,3,4- tetrahydroisoquinoline. (nii.ac.jp)
Oxidative stress is proposed also as a mechanism of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)- and manganese (Mn)-induced neuronal death. (deepdyve.com)
The 1-methyl-4-phenyl-pyridinium ion (MPP(+)), an active metabolite of the neurotoxin, N-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP), induces death in rat pheochromocytoma (PC12) cells, suggesting a cell model of Parkinson's disease (PD). (biomedsearch.com)

The current contribution uses the group's isolated squid axoplasm system to look at the effects of the Parkinson disease-causing toxin 1-methyl-4-phenylpyridinium (MPP+). (alzforum.org)
Using Xenopus oocytes injected with Aqp9 cRNA, we show that AQP9 is permeable to the parkinsonogenic toxin 1-methyl-4-phenylpyridinium (MPP+). (uio.no)

Toxicity of the 1-methyl-4-phenyl-2,3-dihydropyridinium and 1-methyl-4-phenylpyridinium species in primary cultures of mouse astrocytes. (aspetjournals.org)
In the concentration range of 0.1-0.25 mM LipC protected neuronal cells against 1-methyl-4-phenylpyridinium (MPP + )-induced toxicity. (springer.com)
This paper describes a microarray study including data quality control, data analysis and the analysis of the mechanism of toxicity (MOT) induced by 1-methyl-4-phenylpyridinium (MPP + ) in a rat adrenal pheochromocytoma cell line (PC12 cells) using bioinformatics tools. (biomedcentral.com)

To investigate the role of nitric oxide (NO)/reactive oxygen species (ROS) redox signaling in Parkinson's disease-like neurotoxicity, we used 1-methyl-4-phenylpyridinium (MPP + ) treatment (a model of Parkinson's disease). (elsevier.com)
In conclusion, Sal prevented MPP+-induced neurotoxicity through upregulation of DJ-1-Nrf2-antioxidant pathway. (hindawi.com)
A similar structure of PQ to MPP + (1-methyl-4-phenylpyridinium) caused PQ-induced neurotoxicity and injury to renal proximal tubules. (rsc.org)

The present in vivo and in vitro findings clearly indicate that the CB 1 receptor possesses anti-inflammatory properties and inhibits microglia-mediated oxidative stress. (jimmunol.org)
In this study, we found that isorhynchophylline (IRN) significantly attenuated 1-methyl-4-phenylpyridinium (MPP + )-induced apoptotic cell death and oxidative stress in PC12 cells. (springer.com)
We found that overexpression of tail interacting protein of 47 kDa (TIP47), but not its truncated form (t-TIP47) protected NIH3T3 cells from hydrogen-peroxide-induced cell death, prevented the hydrogen-peroxide-induced mitochondrial depolarization determined by 5,50,6,60-tetrachloro-1,10,3,30-tetraethyl-benzimidazolylcarbocyanine iodide (JC1), while suppression of TIP47 in HeLa cells facilitated oxidative-stress-induced cell death. (biomedsearch.com)

Parkinson's disease is a neurodegenerative disease that affects 1-2% of people above 65 years of age. (biomedcentral.com)
We now report that minocycline, a semisynthetic tetracycline, recently shown to have neuroprotective effects in animal models of stroke/ischemic injury and Huntington's disease, prevents nigrostriatal dopaminergic neurodegeneration in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. (pnas.org)
Several neurotoxins induce Parkinson's-like neuropathology in animals, including the neurotoxins 6-hydroxydopamine and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) ( 3 ). (pnas.org)
Inflammatory responses in the brain parenchyma have been associated with the etiopathogenesis of different neurological disorders, including central nervous system (CNS) infection, brain ischemia, multiple sclerosis, Alzheimer's disease, and Parkinson's disease [ 1 - 7 ]. (hindawi.com)
Neuronal accumulation of 1-methyl-4-phenylpyridinium ion (MPP+), the metabolite of neural toxin, 1-methyl-4-phenyl-1,2,3,6-tetrahyropyridine (MPTP), induces a rapid depletion of cellular ATP level and loss of neuronal cell viability which simulates human Parkinson's disease (PD). (hanyang.ac.kr)
In this study, using the well-established LPS and the 1-methyl-4-phenylpyridinium-mediated models of Parkinson's disease, we demonstrate that TGF-β1 exerts significant neuroprotection in both models via its anti-inflammatory properties. (jimmunol.org)
Substantial evidence now demonstrates that microglia-mediated inflammatory processes play an important role in the pathogenesis of several neurodegenerative diseases, including Parkinson's disease (PD), 3 Alzheimer's disease, multiple sclerosis, and the AIDS dementia complex ( 1 , 2 , 3 ). (jimmunol.org)
Parkinson's disease (PD) is the second most common neurodegenerative disorder, affecting more than 1% of humans over 60 years of age [ 1 , 2 ]. (hindawi.com)
Aldehyde Dehydrogenase 1 making molecular inroads into the differential vulnerability of nigrostriatal dopaminergic neuron subtypes in Parkinson's disease. (springer.com)
Parkinson's disease (PD) is a common neurodegenerative disease that mainly occurs in the elderly [ 1 , 2 ]. (mdpi.com)
Loss of the Parkinson's disease-linked gene DJ-1 perturbs mitochondrial dynamics. (biomedsearch.com)
BRUP-1, an intracellular bilirubin modulator, exerts neuroprotective activity in a cellular Parkinson's disease model. (amedeo.com)

After parenteral administration, MPTP readily enters the brain and is metabolized by astroglia to 1-methyl-4-phenylpyridinium (MPP + ) ( 6 ). (pnas.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)
Environmental toxins mimicking PD such as N -methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or its active derivative, 1-methyl-4-phenylpyridinium ion (MPP + ), also disrupt axonal function. (jneurosci.org)
Does 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) cause Parkinson disease (PD)? (medscape.com)
Several individuals were identified who developed parkinsonism after self-injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). (medscape.com)
MPTP crosses the blood-brain barrier and is oxidized to 1-methyl-4-phenylpyridinium (MPP+) by monoamine oxidase (MAO)-B. (medscape.com)
Permanent human parkinsonism due to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): seven cases. (medscape.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)
We have recently shown that Mn and the MPTP analogue 1-methyl-4-(2′-ethylphenyl)-1,2,3,6-tetrahydropyridine (2′Et-MPTP), which is metabolized by MAO-A to 1-methyl-4-(2′-ethylphenyl)-pyridinium ion, induce apoptosis in PC12 cells. (deepdyve.com)

Furthermore, silencing of DJ-1 significantly suppressed the decrease of apoptosis induced by Sal in MPP+-treated SH-SY5Y cells. (hindawi.com)
TY - JOUR T1 - Implication of the c-Jun-NH2-terminal kinase pathway in the neuroprotective effect of puerarin against 1-methyl-4-phenylpyridinium (MPP+)-induced apoptosis in PC-12 cells. (unboundmedicine.com)
Furthermore, IRN inhibits MPP + -triggered apoptosis signal-regulating kinase 1 (ASK1)/c-Jun N-terminal Kinase (JNK) signaling-mediated mitochondria-dependent apoptosis pathway. (springer.com)
Our results revealed that bee venom pretreatment (1-100ng/ml) increased the cell viability and decreased apoptosis assessed by DNA fragmentation and caspase-3 activity assays in MPP(+)-induced cytotoxicity in SH-SY5Y cells. (blogspot.com)

In the current study, the potential of two omega-6 fatty acids (i.e. arachidonic acid and linoleic acid) in alleviating 1-methyl-4-phenylpyridinium (MPP + )-induced cytotoxicity in PC12 cells was examined. (biomedcentral.com)
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 promoting effect of hydrogen peroxide (H2O2) against the cytotoxicity of 1-methyl-4-phenylpyridinium (MPP+) in differentiated PC12 cells was assessed by measuring the effect on the mitochondrial membrane permeability. (koreamed.org)

2018): 1-10. (rit.edu)

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)
[1] This is accomplished by blocking the binding site of the substrate - the active site - by some means. (wikipedia.org)
[10] Competitive substrates, such as 4-substituted benzaldehydes for mushrooms, compete with the substrate lowering the amount of the monophenols that bind. (wikipedia.org)

Cultured PC12 cells were either treated with MPP + alone or co-treated with one of the omega-6 fatty acids for 1 day. (biomedcentral.com)
We examined effects of three structurally related pyridinium compounds, 1-methyl-4-phenylpyridinium (MPP + ), paraquat, and l-methyl-4-(4'- nitrophenyl) pyridinium (analog 1), on the energy metabolism in pheochromocytoma PC12 cells. (elsevier.com)
OBJECTIVE To observe the effect of dihydromyricetin (DMY) on cell injury induced by 1-methyl-4-phenylpyridinium (MPP+) in PC12 cells and explore the possible mechanism. (bvsalud.org)
METHODS After being pretreated with DMY 5, 10, 20, 40 and 80 μmol · L-1 for 0.5 h, PC12 cells were incubated with DMEM culture medium including autophagy inhibitor 3-methyladenine (3-MA) 10 mmol · L-1 and MPP+500μmol·L-1 for 48 h. (bvsalud.org)
IRN-mediated attenuation of endoplasmic reticulum modulator caspase-12 activation was abolished by diphenyleneiodonium (DPI) or IRE-1α shRNA, but not by SP600125 or pifithrin-α in MPP + -treated PC12 cells. (springer.com)

The loss of dopaminergic afferents from the substantia nigra to the striatum and putamen results in extrapyramidal motor dysfunction, including tremor, rigidity, and bradykinesia ( 1 ). (pnas.org)

Oxaliplatin, however, exhibits a different anticancer spectrum from that of cisplatin ( 3 , 4 ). (aacrjournals.org)
Because cisplatin and oxaliplatin target similar DNA sites for binding and form similar types of DNA adducts ( 9 - 13 ), mainly 1,2-intrastrand and 1,3-intrastrand cross-links involving purine nucleotides, the mechanisms responsible for their distinct tumor specificities may involve events other than their interaction with and binding to DNA. (aacrjournals.org)

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)

The neuroprotective effect of minocycline is associated with marked reductions in inducible NO synthase (iNOS) and caspase 1 expression. (pnas.org)

Cultures of bovine adrenomedullary chromaffin cells accumulated 1-methyl-4-phenylpyridinium (MPP+) in a time- and concentration-dependent manner by a process that was prevented by desmethylimipramine. (pnas.org)

British Journal of Pharmacology , 159 (4), 898-908. (eur.nl)

IRN markedly reduced MPP + -induced-ERS responses, indicative of inositol-requiring enzyme 1 (IRE1) phosphorylation and caspase-12 activation. (springer.com)
Inhibitions of MPP + -induced both cytochrome c release and caspase-9 activation by IRN were blocked by pre-treatment with DPI or pifithrin-α, but not by IRE-1α shRNA. (springer.com)

Taken together, our results show that TGF-β1 exerted potent anti-inflammatory and neuroprotective properties, either through the prevention of the direct activation of microglia by LPS, or indirectly through the inhibition of reactive microgliosis elicited by 1-methyl-4-phenylpyridinium. (jimmunol.org)

The synthesis involves reacting 4-phenylpyridine with methyl iodide in acetonitrile solvent at reflux for 24 hours. (wikipedia.org)

4] "Wide variety of locations for rodent MATE1, a transporter protein that mediates the final excretion step for toxic organic cations. (tcdb.org)

The objective of the present study is to investigate the neuroprotective mechanism of bee venom against Parkinsonian toxin, 1-methyl-4-phenylpyridine (MPP(+)), in SH-SY5Y human neuroblastoma cells. (blogspot.com)

2017): 1-10. (rit.edu)
4 (2017): 393-401. (rit.edu)
1 (2017): 15-33. (rit.edu)

Platinum-based drugs are among the most active anticancer agents, and cisplatin represents one of the three most widely used cancer chemotherapeutics ( 1 ). (aacrjournals.org)

The biochemical and toxic effects of the two monoamine oxidase-generated metabolites of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine were investigated using primary cultures of mouse astrocytes. (aspetjournals.org)
After the addition of equimolar concentrations (25 microM) of these metabolites, namely 1-methyl-4-phenyl-2,3-dihydropyridinium (MPDP+) ion or 1-methyl-4-phenylpyridinium (MPP+) ion, similar levels of MPP+ accumulated within the astrocytes. (aspetjournals.org)

These uptake mechanisms are also important for disposition and action of a broad variety of cardiovascular drugs frequently used concomitantly in patients with type 2 diabetes (e.g., statins, ACE inhibitors, and angiotensin type 1 receptor blockers) ( 12 ). (diabetesjournals.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)
Culturing neonatal rat islets in the presence of low d -glucose concentrations (2.8-5.6 mmol/l) and 1 mmol/l H 2 O 2 increased the d -glucose uptake by islets sixfold compared to control levels. (chemweb.com)
Upon binding to this site, Zn2+ causes inhibition of [3H]1-methyl-4-phenylpyridinium ([3H]MPP+) uptake. (amphetamines.com)

The industrial synthesis of MPP+ for sale as the herbicide cyperquat used methyl chloride as the source of the methyl group. (wikipedia.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)
Annonacin is 100 times more toxic than 1-methyl-4-phenylpyridinium (MPP+), another potent mitochondrial complex I inhibitor. (wikipedia.org)
BAK, another antimicrobial QUATS that is structurally similar to CPC, and the pesticide rotenone, a known complex 1 inhibitor, also showed mitochondrial inhibitory and antiestrogenic effects. (nih.gov)
The results show: (1) XE-991 (Kv7.1-7.4-inhibitor), but not chromanol 293B (Kv7.1-inhibitor), increased tyramine-stimulated norepinephrine overflow and epinephrine secretion in both sexes in SHR, but not WKY. (uio.no)

Reserpine precludes the storage of monoamines through the blockage of the synaptic vesicles transporters [ 1 ]. (omicsonline.org)

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)
Phytic acid suppresses 1-methyl-4-phenylpyridinium ion-induced hydroxyl radical generation in rat striatum. (wikiversity.org)

Striatal dopaminergic depletion following intranigral infusion of MPP + in rats was significantly attenuated by NG, SNAP and SIN-1, but not by SNP. (elsevier.com)
Strain susceptibility and resistance to 1,2-dimethylhydrazine-induced enteric tumors in germfree rats (40146). (cdc.gov)
In this study, the status of a matrix glycoprotein fibronectin (FN) and its receptor α 5 β 1 integrin in the articular cartilage in collagen type II-induced experimental arthritis in rats, as well as in synovial fluid from osteoarthritic patients was investigated. (niscair.res.in)
To evaluate whether metformin restores leptin sensitivity in aged rats with leptin resistance, we measured leptin sensitivity in aged (2 year old) and adult (5 month old) rats after 4. (koreamed.org)

Kanthasamy, A. G. and Reddy, M. B. ( 2008 ) Abstract Toxicology 245 (1-2):101 - 108. (wikiversity.org)

for OCT1, 1-methyl-4-phenylpyridinium [MPP + ] and metformin). (diabetesjournals.org)

Expressions of autophagy related protein , Beclin-1 , microtubule-associated protein light chain 3 (LC3) and p62 were measured by Western blotting . (bvsalud.org)
The K m values for acyclovir, ganciclovir, and penciclovir transport were 94, 264, and 277 μM, respectively, and transport efficiencies were relatively high (6-24 μl · min −1 · mg protein −1 ). (aspetjournals.org)
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)
Under basal conditions, Nrf2 is sequestered in the cytoplasm via its interaction with the repressor Keap1 (Kelch-like ECH-associating protein 1), which facilitates its polyubiquitylation and proteasome-mediated degradation ( Fig. 1A ). (biologists.org)
The ubiquitin-proteasome system controls protein turnover and regulates a variety of signaling pathways and cellular processes, from cell proliferation to differentiation to death ( 1 ). (aacrjournals.org)
The Skp1-Cullin1-F-box-protein (SCF) E3 ubiquitin ligases are multiunit complexes and consist of scaffold proteins (cullin 1-cullin 7), RING-finger proteins (RBX1/ROC1 or RBX2/SAG), adaptor proteins (e.g. (aacrjournals.org)

1988. Species-specific response to the rodent carcinogens 1,2-dimethylhydrazine and 1,2-dibromo-3-chloropropane in rodent bone-marrow micronucleus assays. (cdc.gov)

But Nrf2 silence did not significantly impact Sal-exhibited effects on DJ-1 expression. (hindawi.com)
First author Gerardo Morfini worked with Rodolfo Llinas and colleagues at the New York University School of Medicine to demonstrate that MPP+ treatment significantly increased dynein-dependent retrograde vesicle transport (away from synapses) and slightly decreased kinesin-1 mediated anterograde transport (toward synapses). (alzforum.org)

Parkinson disease (PD) is one of the most common neurologic disorders, affecting approximately 1% of individuals older than 60 years and causing progressive disability that can be slowed, but not halted, by treatment. (medscape.com)
Parkinson disease is recognized as one of the most common neurologic disorders, affecting approximately 1% of individuals older than 60 years. (medscape.com)
Cortico-Subcortical Dynamics in Parkinson¿s Disease, 1-8. (wikipedia.org)

0.9 μM), and additional findings supported inhibition of mitochondrial complex 1 as the underlying mechanism for these effects. (nih.gov)

It is now well established that drug transporters are major determinants of drug disposition and effects ( 1 , 2 ). (diabetesjournals.org)
The organic anion transporters 1 and 3 (OAT1 and OAT3) and organic cation transporter 2 (OCT2) are important for renal tubular drug secretion. (aspetjournals.org)
Using the stopped flow tubular microperfusion method, cultured renal epithelial cells, and isolated membrane vesicles, it was suggested that two functionally distinct organic cation transporters were expressed in the basolateral and brush border membranes, respectively ( 1 , 2 ). (asnjournals.org)

MPP+ (1-methyl-4-phenylpyridinium) is a positively charged organic molecule with the chemical formula C12H12N+. (wikipedia.org)
Recently, in silico homology screening of the human cDNA database identified a H + /organic cation antiporter, human multidrug and toxin extrusion 1 (hMATE1), from the human brain using the NorM Na + /multidrug antiporter in Vibrio parahaemolyticus as a reference ( 12 ). (asnjournals.org)

Although activation of microglia serves an important protective function in immune surveillance by removing foreign microorganisms ( 4 ), overactivation of microglia followed by overproduction of proinflammatory factors has been shown to result in neuronal death in the brain ( 5 , 6 ). (jimmunol.org)

Rather than unveiling their physiological properties and functions in normal brain tissue, the synucleins are mostly exploited as biomarkers for neurodegenerative diseases since the discovery of their involvement in proteinaceous aggregation in patients with Alzheimer's disease (AD) [ 1 ]. (intechopen.com)

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)

mPGES-1 is an inducible enzyme and is expressed also in activated microglia [ 15 , 16 ]. (hindawi.com)
The subjects were genotyped using PCR amplification of the exon 4 region of the UCP2 gene followed by digestion with the restriction enzyme Ecl HK1. (chemweb.com)
Currently, it is hypothesized that the anticarcinogenic effects of cruciferous vegetables may be due to their relatively high levels of glucosinolates, which, following hydrolysis by the enzyme myrosinase, result in the formation of isothiocyanates ( 1 , 7 ). (aacrjournals.org)

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)
For example, Daryl Bosco of the University of Massachusetts in Worcester presented data showing that two proteins associated with amyotrophic lateral sclerosis (ALS)-superoxide dismutase 1 (SOD1) and Fused in Sarcoma (FUS)-inhibit FAT. (alzforum.org)
Among them, autophagy - an evolutionary conservative intracellular mechanism based on the elimination of macromolecular components of cytoplasm, especially proteins with a long half-life and whole organelles - has a great application potential in controlling the processes of neurodegeneration [4-11]. (termedia.pl)
During the assembly stage of the primary cilium, cilia-targeting proteins are transported from the Golgi to the basal body via vesicular transport, and then to the ciliary tip along the axoneme via intraflagellar transport (IFT) 1 . (nature.com)

Anatomy12

Diseases5

Chemicals and Drugs28

Analytical, Diagnostic and Therapeutic Techniques and Equipment4

Phenomena and Processes4

Anthropology, Education, Sociology and Social Phenomena1

Health Care2

Poly(ADP-ribose) polymerase activation mediates 1-methyl-4-phenyl-1, 2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism. (1/255)

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

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

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

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

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

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

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

1-Methyl-4-phenylpyridinium

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

MPTP Poisoning

Organic Cation Transport Proteins

Organic Cation Transporter 1

Pyridinium Compounds

Vesicular Biogenic Amine Transport Proteins

Rotenone

Herbicides

Catecholamine Plasma Membrane Transport Proteins

Neurotoxins

Dopamine Agents

Equilibrative Nucleoside Transport Proteins

Dopamine

Parkinson Disease, Secondary

Dopaminergic Neurons

Vesicular Monoamine Transport Proteins

Tetrabenazine

Mesencephalon

Monoamine Oxidase

Dopamine Plasma Membrane Transport Proteins

3,4-Dihydroxyphenylacetic Acid

Parkinson Disease

Membrane Transport Proteins

Parkinsonian Disorders

Cations

Substantia Nigra

Tyrosine 3-Monooxygenase

Neuroprotective Agents

Neurons

PC12 Cells

Biological Transport

Corpus Striatum

Nerve Degeneration

Mitochondria

Cell Death

NG-Nitroarginine Methyl Ester

Reactive Oxygen Species

Adrenal Medulla

Chromaffin Granules

Chromaffin Cells

Chromaffin System

Catecholamines

Digitonin

Cerebellum

Cyclic GMP

Nitric Oxide

Equipment Safety

Device Approval

United States Food and Drug Administration

Therapeutic Equivalency

Kidney Transplantation

Hematopoietic Stem Cell Mobilization

Substrate Specificity

Poly(ADP-ribose) polymerase activation mediates 1-methyl-4-phenyl-1, 2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism. (1/255)

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

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

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

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

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

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

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

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