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.Adrenal Medulla: 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.Chromaffin Granules: 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.Chromaffin Cells: 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.Chromaffin 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.Catecholamines: A general class of ortho-dihydroxyphenylalkylamines derived from tyrosine.Digitonin: 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.Cerebellum: 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.Cyclic GMP: 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)Nitric Oxide: 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.Equipment Safety: Freedom of equipment from actual or potential hazards.Device Approval: 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.United States Food and Drug Administration: 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.Therapeutic Equivalency: 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.Kidney Transplantation: The transference of a kidney from one human or animal to another.Hematopoietic Stem Cell Mobilization: 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.Substrate Specificity: 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)

TY - JOUR. T1 - Involvement of nitric oxide/reactive oxygen species signaling via 8-nitro-cGMP formation in 1-methyl-4-phenylpyridinium ion-induced neurotoxicity in PC12 cells and rat cerebellar granule neurons. AU - Masuda, Kumiko. AU - Tsutsuki, Hiroyasu. AU - Kasamatsu, Shingo. AU - Ida, Tomoaki. AU - Takata, Tsuyoshi. AU - Sugiura, Kikuya. AU - Nishida, Motohiro. AU - Watanabe, Yasuo. AU - Sawa, Tomohiro. AU - Akaike, Takaaki. AU - Ihara, Hideshi. PY - 2018/1/15. Y1 - 2018/1/15. N2 - To investigate the role of nitric oxide (NO)/reactive oxygen species (ROS) redox signaling in Parkinsons disease-like neurotoxicity, we used 1-methyl-4-phenylpyridinium (MPP+) treatment (a model of Parkinsons disease). We show that MPP+-induced neurotoxicity was dependent on ROS from neuronal NO synthase (nNOS) in nNOS-expressing PC12 cells (NPC12 cells) and rat cerebellar granule neurons (CGNs). Following MPP+ treatment, we found production of 8-nitroguanosine 3′,5′-cyclic monophosphate (8-nitro-cGMP), a ...
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces parkinsonism in humans after its oxidation into 1-methyl-4-phenylpyridinium ion (MPP+) by type B monoamine oxidase. The 1-amino analogues of MPTP and MPP+, 1-amino-4-phenyl-1,2,3, 6-tetrahydropyridine (APTP) and 1-amino-4-phenylpyridinium ion (APP+), were synthesized, and their cytotoxicity to clonal pheochromocytoma PC12 cells was examined using a tetrazolium formazan assay. After ...
My laboratory is interested in the molecular and cellular bases of neurological and neuropsychiatric disorders. For example, atypical dopamine function has been implicated in disorders such as Parkinsons disease, drug addiction, affective disorders and Schizophrenia. A current lab emphasis is in determining the mechanisms of cell death in Parkinsons disease. We are examining the biochemical and genetic events associated with parkinsonian models in vivo and in primary cultures of dopaminergic neurons. Microarray analysis is being used to globally determine which signaling pathways are utilized by parkinsonism-inducing agents as well as the known mutations. Enhanced understanding of the common and distinct cell death mechanisms associated with these toxins and genes may identify unique cellular targets for the generation of novel therapeutic interventions. In other studies, we are using homologous recombination and recombineering to create animal models in which gene expression in dopaminergic ...
My laboratory is interested in the molecular and cellular bases of neurological and neuropsychiatric disorders. For example, atypical dopamine function has been implicated in disorders such as Parkinsons disease, drug addiction, affective disorders and Schizophrenia. A current lab emphasis is in determining the mechanisms of cell death in Parkinsons disease. We are examining the biochemical and genetic events associated with parkinsonian models in vivo and in primary cultures of dopaminergic neurons. Microarray analysis is being used to globally determine which signaling pathways are utilized by parkinsonism-inducing agents as well as the known mutations. Enhanced understanding of the common and distinct cell death mechanisms associated with these toxins and genes may identify unique cellular targets for the generation of novel therapeutic interventions. In other studies, we are using homologous recombination and recombineering to create animal models in which gene expression in dopaminergic ...
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In view of the neurotoxic properties of 1-methyl-4-phenylpyridinium (MPP+), the monoamine oxidase-B-generated metabolite of the Parkinsonian agent 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (Kalgutkar et al., 2001), the identification of MPP+-like HPP+ and RHPP+ metabolites in significant quantities in the urine (Subramanyam et al., 1991b), plasma (Avent et al., 1997), and post-mortem brain samples (Eyles et al., 1997) in schizophrenic patients treated with HP is of neurotoxicological importance especially in the pathogenesis of HP-induced TD. Additional support for this proposal is evident from the observations that HPP+ displays MPP+-like neurotoxicity in vivo as well as in vitro (Bloomquist et al., 1994).. Although glucuronidation and reduced HP formation constitute the major routes of HP clearance in humans, the wide interindividual variations in HP oral clearance have been mainly attributed to the "minor" P450-catalyzed biotransformation pathways (30% of overall HP metabolism) (Kudo and ...
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Plasmid pDONR223-MPP5 from Dr. William Hahns lab contains the insert MPP5 and is published in Nature. 2010 Nov 24. ():. This plasmid is available through Addgene.
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4-hydroxy-4-methyl-2,5-cyclohexadien-1-one - chemical structural formula, chemical names, chemical properties, synthesis references
The organic cation transporter OCT1 (SLC22A1) mediates the uptake of vitamin B1, cationic drugs, and xenobiotics into hepatocytes. Nine percent of Caucasians lack or have very low OCT1 activity due to loss-of-function polymorphisms in OCT1 gene. Here we analyzed the global genetic variability in OCT1 to estimate the therapeutic relevance of OCT1 polymorphisms in populations beyond Caucasians and to identify evolutionary patterns of the common loss of OCT1 activity in humans. We applied massively parallel sequencing to screen for coding polymorphisms in 1,079 unrelated individuals from 53 populations worldwide. The obtained data was combined with the existing 1000 Genomes data comprising an additional 1,092 individuals from 14 populations. The identified OCT1 variants were characterized in vitro regarding their cellular localization and their ability to transport 10 known OCT1 substrates. Both the population genetics data and transport data were used in tandem to generate a world map of loss of OCT1
The organic cation transporter OCT1 (SLC22A1) mediates the uptake of vitamin B1, cationic drugs, and xenobiotics into hepatocytes. Nine percent of Caucasians lack or have very low OCT1 activity due to loss-of-function polymorphisms in OCT1 gene. Here we analyzed the global genetic variability in OCT1 to estimate the therapeutic relevance of OCT1 polymorphisms in populations beyond Caucasians and to identify evolutionary patterns of the common loss of OCT1 activity in humans. We applied massively parallel sequencing to screen for coding polymorphisms in 1,079 unrelated individuals from 53 populations worldwide. The obtained data was combined with the existing 1000 Genomes data comprising an additional 1,092 individuals from 14 populations. The identified OCT1 variants were characterized in vitro regarding their cellular localization and their ability to transport 10 known OCT1 substrates. Both the population genetics data and transport data were used in tandem to generate a world map of loss of OCT1
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Novel palladium(ii) and platinum(ii) complexes of 5,5-diethylbarbiturate (barb) with 2-phenylpyridine (Hppy), 2,2-bipyridine (bpy) and 2,2-dipyridylamine (dpya) have been prepared and characterized by elemental analysis, IR, UV-Vis, NMR and ESI-MS. Single-crystal diffraction measurements show that complex consists of binuclear [Pd2(μ-barb-κN,O)2(ppy-κN,C)2] moieties, while complexes are mononuclear, [M(barb-κN)2(L-κN,N)] (L = bpy or dpya). has a composition of [Pt(dpya-κN,N)2][Ag(barb-κN)2]2·4H2O and was assumed to have a structure of [Pt(barb-κN)(Hppy-κN)(ppy-κN,C)]·3H2O. The complexes were found to exhibit significant DNA binding affinity by a non-covalent binding mode, in accordance with molecular docking studies. In addition, complexes and displayed strong binding with supercoiled pUC19 plasmid DNA. Cellular uptake studies were performed to assess the subcellular localization of the selected complexes. A moderate radical scavenging activity of and was confirmed by DPPH and ABTS tests
Kidney-specific expression of human organic cation transporter 2 (OCT2/SLC22A2) is regulated by DNA methylation - BioChain Institute Inc.
Cerebellar granule cells are susceptible to the excitotoxin glutamate, which acts at N-methyl-D-aspartate (NMDA) receptors, as well as the neurotoxin 1-methyl-4-phenylpyridinium ion (MPP+), the active cytotoxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Paradoxically, preincubation of cultured cerebellar granule cells with low concentrations of NMDA or glutamate markedly antagonizes the neurotoxicity resulting from subsequent exposure to toxic concentrations of either MPP+ or glutamate. The neuroprotective effects of NMDA and glutamate against MPP+ toxicity are observed at agonist concentrations as low as 1 microM, are blocked by specific NMDA receptor antagonists, and require at least 30 min to develop fully. Moreover, NMDA receptor-mediated neuroprotection is prevented by the RNA synthesis inhibitor actinomycin D or the protein synthesis inhibitor cycloheximide. Thus, in cerebellar granule cells activation of NMDA receptors by glutamate can result in either ...
We have previously demonstrated the unexpected neuroprotection of the anti-cancer agent SU4312 in cellular models associated with Parkinsons disease (PD). However, the precise mechanisms underlying its neuroprotection are still unknown, and the effects of SU4312 on rodent models of PD have not been characterized. In the current study, we found that the protection of SU4312 against 1-methyl-4-phenylpyridinium ion (MPP(+))-induced neurotoxicity in PC12 cells was achieved through the activation of transcription factor myocyte enhancer factor 2D (MEF2D), as evidenced by the fact that SU4312 stimulated myocyte enhancer factor 2 (MEF2) transcriptional activity and prevented the inhibition of MEF2D protein expression caused by MPP(+), and that short hairpin RNA (ShRNA)-mediated knockdown of MEF2D significantly abolished the neuroprotection of SU4312 ...
A thin film of triphenylamine dimer, N,N′-bis(3-methylphenyl)-N,N′-bis(phenyl)-benzidine (TPD), doped with fac tris(2-phenylpyridine) iridium (Ir(ppy)3) and platinum octaethyl porphine (PtOEP) is char
Complete information for OTX2P1 gene (Pseudogene), Orthodenticle Homeobox 2 Pseudogene 1, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Within SWECLIM a 3D fully coupled ice-ocean model has been developed based on the massively parallel OCCAM code from Southampton. Compared to the global OCCAM the model has to be adopted to Baltic Sea conditions with implementations of high-frequent atmospheric forcing fields in connection with adequate bulk formulae for wind stress, heat uxes and freshwater uxes, solar radiation, river runoff, active open boundary conditions, a second-order moment turbulence closure scheme and a dynamic-thermodynamic sea ice model. Thereby, state-of-the-art sub-models and parameterizations have been used. RCO is the first 3D coupled ice-ocean model for the Baltic Sea with the above mentioned specifications suitable for use on mpp computers like CRAY-T3Es. Thus, a milestone for 3D ocean model development has been set. No other model is as fast as RCO. The performance has been improved significantly using advanced algorithms to optimize processor maps. This guarantees work load balance between the different ...
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2-((1-benzenesulfonylpyrrolidine-2-carbonyl)amino)-4-(4-methyl-2-(methyl-(2-(4-(3-o-tolylureido)phenyl)acetyl)amino)pentanoylamino)butyric ...
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ethyl (2E,4E,6E,8E)-3-methyl-9-phenyl-2,4,6,8-nonatetraenoate - chemical structural formula, chemical names, chemical properties, synthesis references
You are viewing an interactive 3D depiction of the molecule [(1r)-2-(6-aminopurin-9-yl)-1-methyl-ethoxy]methyl-[hydroxy(phosphonooxy)phosphoryl]oxy-phosphinic acid (C9H16N5O10P3) from the PQR.
Solute carrier family 22 member 3 (SLC22A3) also known as the organic cation transporter 3 (OCT3) or extraneuronal monoamine transporter (EMT) is a protein that in humans is encoded by the SLC22A3 gene.[1][2][3] Polyspecific organic cation transporters in the liver, kidney, intestine, and other organs are critical for elimination of many endogenous small organic cations as well as a wide array of drugs and environmental toxins. This gene is one of three similar cation transporter genes located in a cluster on chromosome 6. The encoded protein contains twelve putative transmembrane domains and is a plasma integral membrane protein.[3] ...
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-PK1 cell line stably transfected with human NET cDNA (LLC-NET). LLC-NET cells transported [3H]NE and [3H]N-methyl-4-phenylpyridinium ([3H]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 of3H-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, [3H]MPP+ proved preferable to ...
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DESCRIPTION (provided by applicant): This project aims to demonstrate that the evolution of plant biosynthetic pathways can be accelerated and driven to favor the synthesis of ligands which interact with a specific human target protein. This is achieved bysubjecting mutant plant cells to selection pressures favoring the survival of mutants with the phenotype of interest. As an example, this approach will be used to optimize pharmacological activity in Lobelia cardinalis, which inhibits the human dopamine transporter (hDAT), putatively by its ability to synthesize the complex alkaloid, lobinaline. A stable transgenic line of L. cardinalis plant cells expressing the hDAT has been established. These cells show increased sensitivity to toxins transported into the cell by the hDAT, including the neurotoxin MPP+. A large, genetically diverse, population of gain-of-function mutants expressing the hDAT has now been generated, and selected on medium containing 100uM MPP+, which kills the vast majority of ...
Red shift of green-emission band has been observed for fac tris(2-phenylpyridine) iridium (Ir(ppy)3) doped in polycarbonate at 8 K during time evolution after 355-nm laser of 1-ns pulse width. We explain the peak shift and vibronic structure of the emission band using the Franck-Condon principle and the model of (1) three zero-field splitting substates of the triplet state, (2) relaxation processes among the three substates, and (3) different Huang-Rhys factors for these substates. Good agreement was obtained between the calculated and measured emission spectra at various delay times.. © 2005 Chinese Optics Letters. PDF Article ...
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CAS NO:896465-66-0; Chemical name:1-Isoamyl-2-methyl-3,3-dibenzyl-5-chloroindolium bromide ; physical and chemical property of 896465-66-0, 1-Isoamyl-2-methyl-3,3-dibenzyl-5-chloroindolium bromide is provided by ChemNet.com
Comprehensive supplier list for Heptanoic acid,4-[[(1,1-dimethylethoxy)carbonyl]amino]-3-hydroxy-6-methyl-, ethyl ester,(3S,4S)-,Heptanoic acid,4-[[(1,1-dimethylethoxy)carbonyl]amino]-3-hydroxy-6-methyl-, phenylester, [S-(R*,R*)]-
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5-methyl-2-oxooxolane-3-carboxylic acid; CAS Number: 25277-91-2; find Enamine-ENAH5802E785 MSDS, related peer-reviewed papers, technical documents, similar products & more at Sigma-Aldrich
Derivatives of (1.1)ferrocenophane, which carry a reactive olefin function at one of the bridges, are useful in attaching the ferrocenophane system to v...
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. The subcellular localization of the incorporated [methyl-3H]MPP+ was examined by differential centrifugation and sucrose density gradient fractionation and was found to be predominantly colocalized with catecholamines in chromaffin vesicles, and negligible amounts were detected within the mitochondrial fraction. When chromaffin cell membranes were made permeable with the detergent digitonin in the absence of calcium, there was no increase in the release of [3H]MPP+, indicating that there is negligible accumulation of the neurotoxin in the cytosol. Simultaneous exposure to digitonin and calcium induced cosecretion of MPP+ and catecholamines. Stimulation of the cells with nicotine released both catecholamines and MPP+ at identical rates and percentages of cellular content in a calcium-dependent ...
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Rat embryonic mesencephalic cultures were employed to evaluate the consequences of adding GM1 ganglioside to cultures lesioned with the selective neurotoxin 1-methyl-4-phenylpyridinium (MPP+). MPP+ reduced dopamine and DOPAC content, dopamine uptake, aromatic L-amino acid decarboxylase activity, and the number of tyrosine hydroxylase- immunopositive neurons. The immunopositive neurons that remained were aberrant. All of these parameters were partially restored by adding GM1 ganglioside to the cultures. The response to GM1 was not altered by prior treatment of the cultures with cytosine beta-D-arabinofuranoside to reduce the number of glial cells. Dopamine uptake activity restored by GM1 was lost if GM1 was removed from the culture.. ...
This innovative text explores the cellular transport of organic cations, from functional and structural properties to pharmacological implications and psychiatric developments. The authoritative chapters introduce organic cation transporters and then proceed to discuss their mechanisms such as
About 40% of all prescribed drugs are cationic at physiological pH and the multidrug Organic Cation Transporters, OCT1 and OCT2, are the initial steps in their...
Lamivudine (3TC), a drug used in the treatment of HIV infection, needs to cross the plasma membrane to exert its therapeutic action. Human Organic cation transporter 1 (hOCT1), encoded by the SLC22A1 gene, is the transporter responsible for its uptake into target cells. As SLC22A1 is a highly polymorphic gene, the aim of this study was to determine how SNPs in the OCT1-encoding gene affected 3TC internalization and its interaction with other co-administered drugs. HEK293 cells stably transfected with either the wild type form or the polymorphic variants of hOCT1 were used to perform kinetic and drug-drug interaction studies. Protein co-immunoprecipitation was used to assess the impact of selected polymorphic cysteines on the oligomerization of the transporter. Results showed that 3TC transport efficiency was reduced in all polymorphic variants tested (R61C, C88R, S189L, M420del, and G465R). This was not caused by lack of oligomerization in case of variants located at the transporter ...
product Name 1-methyl-aminomethyl-naphthalene Synonyms 1-Methyl-Aminomethylnaphthalene; N-Methyl-1-Naphthalene Methylamine; N-Methyl-1-Naphthalenemethyl Amine; N-Methyl-1-Naphthalenemethylamine; N-Methyl-1-Naphthylmethylamine;...
Complete information for MPP5 gene (Protein Coding), Membrane Palmitoylated Protein 5, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
... (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 ...
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 ...
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 ( ...
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 ...
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- ...
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, ...
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 ...
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 ...
... (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). ...
... 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 --- ...
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 ...
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 ...
"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 ...
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] ...
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 ...
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 ...
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 ...
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 ...
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- ...
... 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 ...
... 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 ...
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.. ...
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 ... Plasma Membrane Cholesterol Regulates the Allosteric Binding of 1-Methyl-4-Phenylpyridinium to Organic Cation Transporter 2 ( ... Plasma Membrane Cholesterol Regulates the Allosteric Binding of 1-Methyl-4-Phenylpyridinium to Organic Cation Transporter 2 ( ...
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 ...
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 ...
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 ...
... 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 ...
... 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 ...
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 ...
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. ...
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;. ...
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. ...
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 ...
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) ...
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 ...
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 ...
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 ( ...
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 ...
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+- ...
Theoretical-Studies On Mechanism Of Mptp Action - Et Interference By Mpp+ (1-Methyl-4-Phenylpyridinium) With Mitochondrial ...
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 ...
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 ...
  • The subcellular localization of the incorporated [methyl-3H]MPP+ was examined by differential centrifugation and sucrose density gradient fractionation and was found to be predominantly colocalized with catecholamines in chromaffin vesicles, and negligible amounts were detected within the mitochondrial fraction. (pnas.org)
  • 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)
  • 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)
  • 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)
  • 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)
  • Using Xenopus oocytes injected with Aqp9 cRNA, we show that AQP9 is permeable to the parkinsonogenic toxin 1-methyl-4-phenylpyridinium (MPP+). (uio.no)
  • 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)
  • Accordingly, environmental exposure to neurotoxic pesticides increases the risk of developing PD, and indeed, intoxication with the dopaminergic toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP) elicits PD in humans, primates, and rodents and represents a well-characterized toxin-based mouse model for PD ( Dauer and Przedborski, 2003 ). (rupress.org)
  • Furthermore, silencing of DJ-1 significantly suppressed the decrease of apoptosis induced by Sal in MPP+-treated SH-SY5Y cells. (hindawi.com)
  • 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, 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)
  • 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)
  • A novel mutation in the NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 4 (Ndufa4) gene links mitochondrial dysfunction to the development of diabetes in a rodent model. (abcam.com)
  • 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)
  • 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)
  • In nanodiscs formed with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine or cholesterol, phosphatidylserine and phosphatidylcholine two low-affinity MPP + binding sites and one high-affinity MPP + binding site per transporter monomer were determined. (aspetjournals.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 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)
  • 1985. Spin-trapping of methyl radical in the oxidative metabolism of 1,2-dimethylhydrazine. (cdc.gov)
  • 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)
  • 1 ] Some speculated that, because certain environmental neurotoxins cause Parkinson s-like ( parkinsonian ) symptoms, some contaminant in the new industrial environment may have increased its prevalence. (chiro.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)
  • Reserpine precludes the storage of monoamines through the blockage of the synaptic vesicles transporters [ 1 ]. (omicsonline.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)
  • 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)
  • 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)
  • 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)
  • Epub 2016 Nov 4. (nih.gov)
  • 2016. Human neural stem cells in patients with chronic ischaemic stroke (PISCES): a phase 1, first-in-man study. (reneuron.com)
  • Cortico-Subcortical Dynamics in Parkinson¿s Disease, 1-8. (wikipedia.org)
  • 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 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 protein1 ). (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)
  • 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)