Labware Additives Identified to Be Selective Monoamine Oxidase-B Inhibitors

Stewart, Jeremy; Drexler, Dieter M.; Leet, John E.; McNaney, Colleen A.; Herbst, John J.

doi:10.1177/1087057114551523

Cited by 6 publications

(7 citation statements)

References 10 publications

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“…Pathologically, GYY co-treatment attenuated the loss of dopaminergic neurons in the SN. Moreover, GYY pretreatment did not alter the striatal MPP + level, which excluded the possibility that GYY inhibited the MPTP metabolism via MAO although sulfides was reported to be MAO inhibitors ( Warenycia et al, 1989 ; Stewart et al, 2014 ). These findings suggest the protective effects of GYY in this PD model.…”

Section: Discussionmentioning

confidence: 95%

GYY4137, an H2S Slow-Releasing Donor, Prevents Nitrative Stress and α-Synuclein Nitration in an MPTP Mouse Model of Parkinson’s Disease

et al. 2017

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The neuromodulator hydrogen sulfide (H2S) was shown to exert neuroprotection in different models of Parkinson’s disease (PD) via its anti-inflammatory and anti-apoptotic properties. In this study, we evaluated the effect of an H2S slow-releasing compound GYY4137 (GYY) on a mouse PD model induced by acute injection with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). GYY was intraperitoneally (i.p.) injected once daily into male C57BL/6J mice 3 days before and 2 weeks after MPTP (14 mg/kg, four times at 2-h intervals, i.p.) administration. Saline was given as a control. Behavioral tests (rotarod, balance beam, and grid walking) showed that 50 mg/kg GYY significantly ameliorated MPTP-caused motor impairments. At lower doses (12.5 and 25 mg/kg) GYY exhibited a less obvious effect. Consistent with this, immunohistochemistry and western blot analysis demonstrated that 50 mg/kg GYY attenuated the loss of tyrosine hydroxylase (TH) positive neurons in the substantia nigra and the decrease of TH expression in the striatum of MPTP-treated mice. Moreover, at this regimen GYY relieved the nitrative stress, as indicated by the decreases in nitric oxide (NO) generation and neuronal NO synthase (nNOS) upregulation elicited by MPTP in the striatum. The suppression of GYY on nNOS expression was verified in vitro, and the results further revealed that Akt activation may participate in the inhibition by GYY on nNOS upregulation. More important, GYY reduced the nitrated modification of α-synuclein, a PD-related protein, in MPTP-induced mice. Overall, our findings suggest that GYY attenuated dopaminergic neuron degeneration and reduced α-synuclein nitration in the midbrain, thus exerting neuroprotection in MPTP-induced mouse model of PD.

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Section: Discussionmentioning

confidence: 95%

GYY4137, an H2S Slow-Releasing Donor, Prevents Nitrative Stress and α-Synuclein Nitration in an MPTP Mouse Model of Parkinson’s Disease

et al. 2017

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“…Over the years, many potential sources of contamination have been suggested but have ultimately been difficult to prove. Occasionally, these contaminants might even behave as specific effectors (e.g., a plastic contaminant 48 ).…”

Section: Sample Contaminants As Nuisancementioning

confidence: 99%

Nuisance Compounds, PAINS Filters, and Dark Chemical Matter in the GSK HTS Collection

et al. 2018

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High-throughput screening (HTS) hits include compounds with undesirable properties. Many filters have been described to identify such hits. Notably, pan-assay interference compounds (PAINS) has been adopted by the community as the standard term to refer to such filters, and very useful guidelines have been adopted by the American Chemical Society (ACS) and subsequently triggered a healthy scientific debate about the pitfalls of draconian use of filters. Using an inhibitory frequency index, we have analyzed in detail the promiscuity profile of the whole GlaxoSmithKline (GSK) HTS collection comprising more than 2 million unique compounds that have been tested in hundreds of screening assays. We provide a comprehensive analysis of many previously published filters and newly described classes of nuisance structures that may serve as a useful source of empirical information to guide the design or growth of HTS collections and hit triaging strategies.

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“…In processing the method development, we recognized that the much leaching of C3:0 and C4:0 from disposable plastic tubes 37,38 . As a result of testing many types of tubes (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

Comprehensive and semi-quantitative analysis of carboxyl-containing metabolites related to gut microbiota on chronic kidney disease using 2-picolylamine isotopic labeling LC-MS/MS

Kanemitsu

Mishima

Maekawa

et al. 2019

Sci Rep

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Carboxyl-containing metabolites, such as bile acids and fatty acids, have many important functions and microbiota is involved in the production of them. In the previous study, we found that the chronic kidney disease (CKD) model mice raised under germ-free conditions provided more severe renal damage than the mice with commensal microbiota. However, the precise influence by the microbiome and carboxyl-containing metabolites to the renal functions is unknown. In this study, we aimed to develop a novel chemical isotope labeling-LC-MS/MS method using the 2-picolylamine and its isotopologue and applied the analysis of effects of microbiome and CKD pathophysiology. The developed semi-quantitative method provided the high accuracy not inferior to the absolute quantification. By comparing of four groups of mice, we found that both microbiota and renal function can alter the composition and level of these metabolites in both plasma and intestine. In particular, the intestinal level of indole-3-acetic acid, short-chain fatty acids and n-3 type of polyunsaturated fatty acid, which play important roles in the endothelial barrier function, were significantly lower in germ-free conditions mice with renal failure. Accordingly, it is suggested these metabolites might have a renoprotective effect on CKD by suppressing epithelial barrier disruption.

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Labware Additives Identified to Be Selective Monoamine Oxidase-B Inhibitors

Cited by 6 publications

References 10 publications

GYY4137, an H2S Slow-Releasing Donor, Prevents Nitrative Stress and α-Synuclein Nitration in an MPTP Mouse Model of Parkinson’s Disease

GYY4137, an H2S Slow-Releasing Donor, Prevents Nitrative Stress and α-Synuclein Nitration in an MPTP Mouse Model of Parkinson’s Disease

Nuisance Compounds, PAINS Filters, and Dark Chemical Matter in the GSK HTS Collection

Comprehensive and semi-quantitative analysis of carboxyl-containing metabolites related to gut microbiota on chronic kidney disease using 2-picolylamine isotopic labeling LC-MS/MS

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