Disease relevance of Cyperquat

• Moreover, Fas engagement directly protects neuronal cells from MPTP/1-methyl-4-phenylpyridinium ion toxicity in vitro [1].
• The neurotoxin 1-methyl-4-phenylpyridinium: a selective cytostatic agent in small-cell lung cancer cell lines with neuroendocrine properties [2].
• The heroin analogue 1-methyl-4-phenylpyridinium, MPP(+), both in vitro and in vivo, produces death of dopaminergic substantia nigral cells by inhibiting the mitochondrial NADH dehydrogenase multienzyme complex, producing a syndrome indistinguishable from Parkinson's disease [3].
• In addition, the sequences obtained are highly homologous to the predicted sequence of a protein from PC12 cells that confers to Chinese hamster ovary cells resistance to 1-methyl-4-phenylpyridinium (MPP+), an agent that causes parkinsonism in model systems, confirming the hypothesis that the protein conferring resistance to MPP+ is a VAT [4].
• TRPC1-mediated inhibition of 1-methyl-4-phenylpyridinium ion neurotoxicity in human SH-SY5Y neuroblastoma cells [5].

Psychiatry related information on Cyperquat

• The acute effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridinium ion (MPP+) on mouse locomotor activity and striatal dopamine (DA) and 5-hydroxytryptamine (5-HT) levels were investigated [6].

High impact information on Cyperquat

• PURPOSE: We designed in vitro and in vivo studies to investigate whether the neuroendocrine features in classic SCLC cell lines were sufficient to make them sensitive to 1-methyl-4-phenylpyridinium (MPP+), a known neurotoxin that destroys nigrostriatal dopaminergic neurons [2].
• 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 [7].
• The resistance of 7-NI-injected mice to MPTP is not due to alterations in striatal pharmacokinetics or content of 1-methyl-4-phenylpyridinium ion (MPP+), the active metabolite of MPTP [8].
• Implanted fibroblasts genetically engineered to produce brain-derived neurotrophic factor prevent 1-methyl-4-phenylpyridinium toxicity to dopaminergic neurons in the rat [9].
• Structural dependence of the inhibition of mitochondrial respiration and of NADH oxidase by 1-methyl-4-phenylpyridinium (MPP+) analogs and their energized accumulation by mitochondria [10].

Chemical compound and disease context of Cyperquat

• Nitric oxide donors protect cultured rat astrocytes from 1-methyl-4-phenylpyridinium-induced toxicity [11].
• 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is known to cause parkinsonism by killing dopaminergic neurons; the toxic substance is a metabolite, 1-methyl-4-phenylpyridinium ion (MPP+) [12].
• Brain-derived neurotrophic factor protects dopamine neurons against 6-hydroxydopamine and N-methyl-4-phenylpyridinium ion toxicity: involvement of the glutathione system [13].
• Evaluation of the protective effect of oestradiol against toxicity induced by 6-hydroxydopamine and 1-methyl-4-phenylpyridinium ion (Mpp+) towards dopaminergic mesencephalic neurones in primary culture [14].
• Our data suggest that although a decreased glutathione content is not likely to be the sole cause of dopaminergic neuronal loss in Parkinson's disease, decreased glutathione content may act in conjunction with other factors such as 1-methyl-4-phenylpyridinium to cause the selective death of dopaminergic neurons [15].

Biological context of Cyperquat

• Regulation of autophagy by extracellular signal-regulated protein kinases during 1-methyl-4-phenylpyridinium-induced cell death [16].
• Inasmuch as oxidative stress has also been implicated in PD, the present study examined transcriptional changes mediated by the Parkinsonism-inducing neurotoxins 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenylpyridinium (MPP+) in a dopaminergic cell line [17].
• On the other hand, transient or permanent transfection of antisense PAG608 cDNA into PC12 cells significantly prevented apoptotic cell death induced by 100 microm 6-OHDA or 200 microm hydrogen peroxide but not by 250 microm 1-methyl-4-phenylpyridinium ion [18].
• 6-Hydroxydopamine but not 1-methyl-4-phenylpyridinium abolishes alpha-synuclein anti-apoptotic phenotype by inhibiting its proteasomal degradation and by promoting its aggregation [19].
• Proteasome-dependent degradation of cyclin D1 in 1-methyl-4-phenylpyridinium ion (MPP+)-induced cell cycle arrest [20].

Anatomical context of Cyperquat

• 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 [21].
• IRIP overexpression inhibited endogenous 1-methyl-4-phenylpyridinium (MPP+) uptake activity in HeLa cells [22].
• Energy-driven uptake of the neurotoxin 1-methyl-4-phenylpyridinium into chromaffin granules via the catecholamine transporter [23].
• When expressed in Madin-Darby canine kidney cells and Xenopus laevis oocytes, PMAT efficiently transports serotonin (K(m) = 114 mum), dopamine (K(m) = 329 mum), and the neurotoxin 1-methyl-4-phenylpyridinium (K(m) = 33 mum) [24].
• Here we report that a combination of 1-methyl-4-phenylpyridinium ion (MPP(+)) or rotenone and proteasome inhibition causes the appearance of alpha-synuclein-positive inclusion bodies [25].

Associations of Cyperquat with other chemical compounds

• 1-Methyl-4-phenylpyridinium (MPP+) levels after MPTP administration were similar in Bcl-2 overexpressing mice and littermates [26].
• Exogenous BDNF treatment produced significant neuroprotection against 1-methyl-4-phenylpyridinium, glutamate, and nitric oxide-induced neurotoxicity in the SN4741 cells [27].
• The transport of TEA by hOCT2-A-transfected cells was saturable with the apparent Km value of 63 microM. hOCT2-A stimulated the uptake of TEA, 1-methyl-4-phenylpyridinium, and cimetidine as well as did hOCT2 [28].
• Transfection of hMATE2-B had no affect on the hMATE2-K-mediated transport of TEA. hMATE2-K also transported cimetidine, 1-methyl-4-phenylpyridinium (MPP), procainamide, metformin, and N1-methylnicotinamide [29].
• In vivo bilateral microdialysis in the rat striatum was used to investigate hydroxyl radical formation under basal conditions and after intrastriatal administration of the neurotoxin, 1-methyl-4-phenylpyridinium (MPP+) [30].

Gene context of Cyperquat

• When expressed in mammalian cells, OCT3 mediates the uptake of the neurotoxin 1-methyl-4-phenylpyridinium (MPP+) and the neurotransmitter dopamine [31].
• Akt1/PKBalpha protects PC12 cells against the parkinsonism-inducing neurotoxin 1-methyl-4-phenylpyridinium and reduces the levels of oxygen-free radicals [32].
• Oxidative stress induced by acute complex I inhibition with 1-methyl-4-phenylpyridinium ion activated biphasically the stress-activated c-Jun N-terminal kinase (JNK) and the early transcription factor nuclear factor-kappaB (NF-kappaB) in SH-SY5Y neuroblastoma cells [33].
• Apoptosis inducing factor mediates caspase-independent 1-methyl-4-phenylpyridinium toxicity in dopaminergic cells [34].
• The role of tissue transglutaminase in 1-methyl-4-phenylpyridinium (MPP+)-induced toxicity in differentiated human SH-SY5Y neuroblastoma cells [35].

Analytical, diagnostic and therapeutic context of Cyperquat

• The neurotoxin 1-methyl-4-phenylpyridinium (MPP+) and other mitochondrial inhibitors (e.g., rotenone or 3-nitropropionic acid) elicited apoptosis in cerebellar granule cell cultures via stimulation of autocrine excitotoxicity [36].
• Uptake and accumulation of 1-methyl-4-phenylpyridinium by rat liver mitochondria measured using an ion-selective electrode [37].
• Cultures of dissociated embryonic rat mesencephalic cells were exposed to 10 microM 1-methyl-4-phenylpyridinium (MPP+), a concentration shown earlier to result in loss of greater than 85% of tyrosine hydroxylase (TH)-positive neurons without affecting the total number of cells observed by phase-contrast microscopy [38].
• Similarly, the differentiated DA neurons were more sensitive to another neurotoxin, 1-methyl-4-phenylpyridinium (MPP+), which is commonly used to induce Parkinsonism in animal models, than were the undifferentiated DA neurons in culture [39].
• Intrastriatal microdialysis in the rat with the corresponding 4-benzyl-1-methylpyridinium ion BMP+ for 60 min, however, causes nerve terminal destruction similar to that observed following a 15-min perfusion with the 1-methyl-4-phenylpyridinium ion MPP+, the monoamine oxidase B (MAO-B) generated metabolite derived from MPTP [40].

References