P19-derived neuronal cells express H, H, and H histamine receptors: a biopharmaceutical approach to evaluate antihistamine agents.

Histamine is a biogenic amine implicated in various biological and pathological processes. Convenient cellular models are needed to screen and develop new antihistamine agents. This report aimed to characterize the response of neurons differentiated from mouse P19 embryonal carcinoma cells to histamine treatment, and to investigate the modulation of this response by antihistamine drugs, vegetal diamine oxidase, and catalase.

Copper complexes for biomedical applications: Structural insights, antioxidant activity and neuron compatibility.

Copper coordinated with amino acid residues is essential for the function of many proteins. In addition, copper complexed to free l-Histidine, as [Cu(His)], is used in the treatment of the neurodegenerative Menkes disease and of cardioencephalomyopathy. This study was aimed to coordinate copper(II) with four small ligands (l-Serine, l-Histidine, Urea and Biuret) and to evaluate structural features, stability, antioxidant activity and neuronal compatibility of the resulting complexes.

Chronic exposure to imidacloprid or thiamethoxam neonicotinoid causes oxidative damages and alters carotenoid-retinoid levels in caged honey bees (Apis mellifera).

Over the last decade, the persistent dwindling of the populations of honey bees has become a growing concern. While this phenomenon is partly attributed to neonicotinoids (NEOCs), chronic exposures to these insecticides at environmentally-relevant concentrations are needed to fully estimate their implications. In this study, honey bees were orally exposed for 10 days to low field-realistic concentrations of NEOCs known for their effects on the cholinergic system (imidacloprid - IMI or thiamethoxam - THM).

The ferroxidase ceruloplasmin influences Reelin processing, cofilin phosphorylation and neuronal organization in the developing brain.

Ceruloplasmin (Cp) is an important extracellular regulator of iron metabolism. We showed previously that it stimulates Reelin proteolytic processing and cell aggregation in cultures of developing neurons. Reelin is a secreted protein required for the correct positioning of neurons in the brain.

Neutral Red versus MTT assay of cell viability in the presence of copper compounds.

Copper is essential for numerous physiological functions, and copper compounds may display therapeutic as well as cytotoxic effects. The MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) assay is a standard test largely used in cytotoxicity studies. This report shows that low micromolar levels of copper compounds such as Cu(II)Urea, Cu(II)Ser and CuCl can interfere with the MTT assay making improper the detection of formazan product of MTT reduction.

Differential effects of retinoids and inhibitors of ERK and p38 signaling on adipogenic and myogenic differentiation of P19 stem cells.

All-trans-retinoic acid (atRA) is an essential signaling molecule in embryonic development. It regulates cell differentiation by activating nuclear retinoic acid receptors (RAR) and retinoid-X receptors (RXR), which both control gene expression. In addition, atRA could act in the cytoplasm by modulating the activity of mitogen-activated protein kinases (MAPK) ERK and p38, which also have a role in cell differentiation.

Oxidation of retinoic acids in hepatic microsomes of wild bullfrogs Lithobates catesbeianus environmentally-exposed to a gradient of agricultural contamination.

Agricultural contaminants are suspected of contributing to the increased incidence of deformities and the decline of amphibians populations worldwide. Many authors have further suggested that a retinoid effect could be implicated in teratogenic mechanisms since the reported deformities resemble those caused by abnormal levels of retinoic acid (RA). We previously reported altered retinoid concentrations in male bullfrogs from the Yamaska River basin (Québec, Canada) associated with moderate-to-high agricultural activity, and the findings were consistent with a possible effect on hepatic RA oxidation.

The NCI-N87 cell line as a gastric epithelial barrier model for drug permeability assay.

The objective of this study was to evaluate the human NCI-N87 cell line as a model for gastric permeability drug studies under pH conditions of the stomach. The optimal conditions that led NCI-N87 cells to form a typical differentiated gastric epithelial barrier were a seeding density of 2.5 × 10⁵ cells/cm² on porous inserts and growth in serum-complemented RPMI-1640 medium until 18-27 days post-confluency.

The effects of nitric oxide-oxidase and putative glutathione-peroxidase activities of ceruloplasmin on the viability of cardiomyocytes exposed to hydrogen peroxide.

Ceruloplasmin (CP), a ferroxidase (EC 1.16.3.

P19 neuronal differentiation and retinoic acid metabolism as criteria to investigate atrazine, nitrite, and nitrate developmental toxicity.

Atrazine and nitrogenous fertilizers are agrochemical contaminants frequently detected in water systems in North America. Several studies reported their ability to affect amphibian and mammalian development. Retinoids, supplied in the diet or synthesized by cells, are essential to embryogenesis.

Skeletal and cardiac myogenesis accompany adipogenesis in P19 embryonal stem cells.

P19 embryonic carcinoma cells resemble normal embryonic stem (ES) cells. They generate cardiac and skeletal myocytes in response to retinoic acid (RA) or oxytocin (OT). RA treatment followed by exposure to triiodothyronine (T3) and insulin induces ES cells differentiation into adipocytes and skeletomyocytes.

Nitric oxide signaling in oxytocin-mediated cardiomyogenesis.

Oxytocin (OT), a hormone recently identified in the heart, induces embryonic and cardiac somatic stem cells to differentiate into cardiomyocytes (CM), possibly through nitric oxide (NO). We verified this hypothesis using P19 cells and P19 Clone 6 derivatives expressing a green fluorescent protein (GFP) reporter linked to cardiac myosin light chain-2v promoter. OT treatment of these cells induced beating cell colonies that were fully inhibited by N,G-nitro-L-arginine-methyl-ester (L-NAME), an inhibitor of NO synthases (NOS), partially reduced by 1400W, an inhibitor of inducible NOS, and ODQ, an inhibitor of NO-sensitive guanylyl cyclases.

Implication of the proprotein convertase NARC-1/PCSK9 in the development of the nervous system.

Neural apoptosis-regulated convertase-1/proprotein convertase subtilisin-kexin like-9 (NARC-1/PCSK9) is a proprotein convertase recently described to play a major role in cholesterol homeostasis through enhanced degradation of the low-density lipoprotein receptor (LDLR) and possibly in neural development. Herein, we investigated the potential involvement of this proteinase in the development of the CNS using mouse embryonal pluripotent P19 cells and the zebrafish as models. Time course quantitative RT-PCR analyses were performed following retinoic acid (RA)-induced neuroectodermal differentiation of P19 cells.

Neuroprotective and cardioprotective actions of an association of pyruvate, vitamin E and fatty acids.

Oxidative stress may involve overproduction of hydrogen peroxide which can generate highly cytotoxic hydroxyl radicals in the presence of ferrous ions. This work demonstrates that TCAT (Tricomponent Antioxidant Therapy), an association of pyruvate, vitamin E and fatty acids, provides neuronal and cardiac protection in oxidative stress, ex vivo. Mouse P19 neuron cultures were exposed for 30 min to low millimolar H2O2 concentrations in the absence or presence of Fe2+.

Oxytocin in cardiac ontogeny.

Previous studies demonstrated the presence of oxytocin (OT) and oxytocin receptors (OTRs) in the heart. The present work provides results supporting a potential role of OT in cardiomyogenesis. Here, we show a maximal OT and OTR protein level in the developing rat heart at day 21 of gestation and postnatal days 1-4, when cardiac myocytes are at a stage of intense hyperplasia.

RhoA/ROCK and Cdc42 regulate cell-cell contact and N-cadherin protein level during neurodetermination of P19 embryonal stem cells.

RhoGTPases regulate actin-based signaling cascades and cellular contacts. In neurogenesis, their action modulates cell migration, neuritogenesis, and synaptogenesis. Murine P19 embryonal stem cells differentiate to neurons upon aggregation in the presence of retinoic acid, and we previously showed that RhoA and Cdc42 RhoGTPases are sequentially up-regulated during neuroinduction, suggesting a role at this very early developmental stage.

Oxidative aggregation of ceruloplasmin induced by hydrogen peroxide is prevented by pyruvate.

Ceruloplasmin (CP) is a blue copper glycoprotein with multiple physiological functions including ferroxidase and oxidase activities. CP is also an important serum oxygen free radical (OFR) scavenger and antioxidant, exerting cardioprotective and antifibrillatory actions. Although it has been reported that CP activities can be inhibited by OFR, the intimate mechanism of this inactivation is still not clear.

Oxytocin induces differentiation of P19 embryonic stem cells to cardiomyocytes.

We recently discovered the existence of the oxytocin/oxytocin receptor (OT/OTR) system in the heart. Activation of cardiac OTR stimulates the release of atrial natriuretic peptide (ANP), which is involved in regulation of blood pressure and cell growth. Having observed elevated OT levels in the fetal and newborn heart at a stage of intense cardiomyocyte hyperplasia, we hypothesized a role for OT in cardiomyocyte differentiation.