High-throughput screening for monoamine oxidase-A and monoamine oxidase-B inhibitors using one-step fluorescence assay.
AuthorsGuang HM, Du GH
JournalActa Pharmacol Sin
PubMed ID16723097
'AIM: To develop high-throughput screening (HTS) assays for monoamine oxidase (MAO)-A and MAO-B inhibitors. METHODS: A fluorescence probe based method measuring MAO-A and MAO-B activity was established and optimized, with its sensitivity, stability and specificity evaluated. Reaction conditions including enzyme sources, substrate concentrations, incubation volume and reaction time in 384-well ... More
Catecholamines regulate the activity, secretion, and synthesis of renalase.
AuthorsLi G, Xu J, Wang P, Velazquez H, Li Y, Wu Y, Desir GV,
JournalCirculation
PubMed ID18299506
'BACKGROUND: We previously identified renalase, a secreted novel amine oxidase that specifically degrades circulating catecholamines. Parenteral administration of either native or recombinant renalase lowers blood pressure, heart rate, and cardiac contractility by metabolizing circulating catecholamines. Renalase plasma levels are markedly reduced in patients with chronic kidney disease. It is not ... More
The PPARgamma agonist pioglitazone is effective in the MPTP mouse model of Parkinson's disease through inhibition of monoamine oxidase B.
AuthorsQuinn LP, Crook B, Hows ME, Vidgeon-Hart M, Chapman H, Upton N, Medhurst AD, Virley DJ,
JournalBr J Pharmacol
PubMed ID18332857
'BACKGROUND AND PURPOSE: The peroxisome proliferator-activated receptor-gamma (PPARgamma) agonist pioglitazone has previously been shown to attenuate dopaminergic cell loss in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson''s disease, an effect attributed to its anti-inflammatory properties. In the present investigation, we provide evidence that pioglitazone is effective in the MPTP mouse ... More
Renalase lowers ambulatory blood pressure by metabolizing circulating adrenaline.
AuthorsDesir GV, Tang L, Wang P, Li G, Sampaio-Maia B, Quelhas-Santos J, Pestana M, Velazquez H,
JournalJ Am Heart Assoc
PubMed ID23130169
'Blood pressure is acutely regulated by the sympathetic nervous system through the action of vasoactive hormones such as epinephrine, norepinephrine, and dopamine. Renalase, a recently described, secreted flavoprotein, acutely decreases systemic pressure when administered in vivo. Single-nucleotide polymorphisms present in the gene are associated with hypertension, cardiac disease, and diabetes. ... More
Quantitative structure-activity relationship and complex network approach to monoamine oxidase A and B inhibitors.
AuthorsSantana L, González-Díaz H, Quezada E, Uriarte E, Yáñez M, Viña D, Orallo F,
JournalJ Med Chem
PubMed ID18834112
'The work provides a new model for the prediction of the MAO-A and -B inhibitor activity by the use of combined complex networks and QSAR methodologies. On the basis of the obtained model, we prepared and assayed 33 coumarin derivatives, and the theoretical prediction was compared with the experimental activity ... More
Synthesis, stereochemical identification, and selective inhibitory activity against human monoamine oxidase-B of 2-methylcyclohexylidene-(4-arylthiazol-2-yl)hydrazones.
AuthorsChimenti F, Maccioni E, Secci D, Bolasco A, Chimenti P, Granese A, Carradori S, Alcaro S, Ortuso F, Yáñez M, Orallo F, Cirilli R, Ferretti R, La Torre F,
JournalJ Med Chem
PubMed ID18666768
'A series of 2-methylcyclohexylidene-(4-arylthiazol-2-yl)hydrazones have been investigated for their ability to inhibit selectively the activity of the human A and B isoforms of monoamine oxidase (MAO). The target compounds, which present a stereogenic center on the cyclohexane ring, were obtained as pure (R) and (S) enantiomers by enantioselective HPLC. The ... More
Metabolism of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine by mitochondrion-targeted cytochrome P450 2D6: implications in Parkinson disease.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxic side product formed in the chemical synthesis of desmethylprodine opioid analgesic, which induces Parkinson disease. Monoamine oxidase B, present in the mitochondrial outer membrane of glial cells, catalyzes the oxidation of MPTP to the toxic 1-methyl-4-phenylpyridinium ion (MPP(+)), which then targets the dopaminergic neurons causing ... More
A one-step fluorometric method for the continuous measurement of monoamine oxidase activity.
AuthorsZhou M, Panchuk-Voloshina N
JournalAnal Biochem
PubMed ID9367499
We have developed a one-step fluorometric method for the measurement of monoamine oxidase (MAO) activity in 96-well microplates with sensitivity 10-fold higher than the conventional spectrophotometric assay method. This assay is based on the detection of H2O2 in a horseradish peroxidase-coupled reaction using N-acetyl-3, 7-dihydroxyphenoxazine (Amplex Red), a highly sensitive ... More
Lipid-lowering drugs in the MPTP mouse model of Parkinson's disease: fenofibrate has a neuroprotective effect, whereas bezafibrate and HMG-CoA reductase inhibitors do not.
AuthorsKreisler A, Gelé P, Wiart JF, Lhermitte M, Destée A, Bordet R
JournalBrain Res
PubMed ID17196944
We tested the ability of simvastatin, atorvastatin, fenofibrate and bezafibrate (two synthetic peroxisome proliferator-activated receptor-alpha (PPAR-alpha) agonists) to prevent dopaminergic cell death in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. Tyrosine hydroxylase (TH) immunochemistry was performed 8 days after acute MPTP intoxication. When orally administered for the week prior ... More
A stable nonfluorescent derivative of resorufin for the fluorometric determination of trace hydrogen peroxide: applications in detecting the activity of phagocyte NADPH oxidase and other oxidases.
AuthorsZhou M, Diwu Z, Panchuk-Voloshina N, Haugland RP
JournalAnal Biochem
PubMed ID9367498
The enzymatic determination of hydrogen peroxide can be accomplished with high sensitivity and specificity using N-acetyl-3, 7-dihydroxyphenoxazine (Amplex Red), a highly sensitive and chemically stable fluorogenic probe for the enzymatic determination of H2O2. Enzyme-catalyzed oxidation of Amplex Red, which is a colorless and nonfluorescent derivative of dihydroresorufin, produces highly fluorescent ... More