Search results for "RATS"
showing 10 items of 3537 documents
Intramitochondrial crystalloids in rat pinealocytes.
1982
In the present study the rare occurrence of intramitochondrial crystalloid inclusions in the rat pinealocytes is described. They lie within the mitochondrial matrix and consist of a lattice of moderately electron-dense lines. Intersections at regular intervals form rhomboid-like subunits. The significance of these inclusions is not known.
Design and synthesis of 1-aryl-5-anilinoindazoles as c-Jun N-terminal kinase inhibitors.
2012
Starting from pyrazole HTS hit (1), a series of 1-aryl-1H-indazoles have been synthesized as JNK3 inhibitors with moderate selectivity against JNK1. SAR studies led to the synthesis of 5r as double digital nanomolar JNK3 inhibitor with good in vivo exposure.
Inhibition of astroglial cell proliferation by alcohols: interference with the protein kinase C-phospholipase D signaling pathway.
2000
Abstract Ethanol inhibits astroglial cell proliferation, an effect that may contribute to the development of alcoholic embryopathy in humans. In the present study, we investigated inhibitory effects of ethanol and butanol isomers (1-, 2- and t -butanol) on astroglial cell proliferation induced by the strongly mitogenic phorbol ester, 4s-phorbol-12α,13s-dibutyrate (PDB). 4s-Phorbol-12α,13s-dibutyrate (PDB) induced a 10-fold increase of [3H]thymidine incorporation in cortical astrocytes prepared from newborn rats (EC 50 : 70 nM) which was blocked by Ro 31-8220, a cell-permeable protein kinase C (PKC) inhibitor. Ethanol blocked PDB-induced astroglial proliferation in a concentration-dependent …
Fluvastatin stabilizes the blood–brain barrier in vitro by nitric oxide-dependent dephosphorylation of myosin light chains
2006
Inhibition of the 3-hydroxy-3-methylglutaryl-coenzyme-A reductase and the downstream mevalonate pathway is in part responsible for the beneficial effects that statins exert on the cardiovascular system. In this study we aimed at analysing the stabilizing effects of fluvastatin on the blood-brain barrier (BBB) integrity, using an in vitro co-culture model of ECV304 and C6, or primary bovine endothelial cells and rat astrocytes. Fluvastatin dose-dependently (1-25 micromol/l) increased barrier integrity as analysed by measurements of transendothelial electrical resistance (TEER). This effect (117.4+/-2.6% at 25 micromol/l) was significantly reduced by the nitric oxide (NO) synthase inhibitor L…
Fluvastatin prevents glutamate-induced blood-brain-barrier disruption in vitro.
2008
Abstract Glutamate is an important excitatory amino acid in the central nervous system. Under pathological conditions glutamate levels dramatically increase. Aim of the present study was to examine whether the HMG-CoA inhibitor fluvastatin prevents glutamate-induced blood-brain-barrier (BBB) disruption. Measurements of transendothelial electrical resistance (TEER) were performed to analyze BBB integrity in an in vitro co-culture model of brain endothelial and glial cells. Myosin light chain (MLC) phosphorylation was detected by immunohistochemistry, or using the in-cell western technique. Intracellular Ca 2+ and reactive oxygen species (ROS) levels were analyzed using the fluorescence dyes …
Synthesis and evaluation of microtubule assembly inhibition and cytotoxicity of prenylated derivatives of cyclo-l-Trp-l-Pro
2000
The synthesis of three isoprenylated derivatives of cyclo-L-Trp-L-Pro is described. These substances have been evaluated for cytotoxic activity in rat normal fibroblast 3Y1 cells and have also been evaluated in vitro for the inhibition of microtubule assembly.
Hydantoin-substituted 4,6-dichloroindole-2-carboxylic acids as ligands with high affinity for the glycine binding site of the NMDA receptor.
2002
A novel series of C-3 substituted 4,6-dichloroindole-2-carboxylic acids was synthesized to investigate the influence of different hydrogen-bond donor and acceptor groups at this specific position on the affinity to the glycine site of the NMDA receptor. These novel 3-indolylmethyl derivatives with ring-open (amines, sulfonamides, amides, ureas) and cyclic substituents (imidazolidin-2-ones, (thio)hydantoins) led to the discovery that compounds bearing a hydantoin substituent at the C-3 position of the indole nucleus are the most promising ones. In this series the hydantoins, ureas, and imidazolidin-2-ones were identified as very potent inhibitors of the binding of the glycine site specific l…
Diacylglycerols containing Omega 3 and Omega 6 fatty acids bind to RasGRP and modulate MAP kinase activation.
2003
We elucidated the effects of different diacylglycerols (DAGs), i.e. 1-stearoyl-2-arachidonoyl-sn-glycerol (SAG), 1-stearoyl-2-docosahexaenoyl-sn-glycerol (SDG), and 1-stearoyl-2-eicosapentaenoyl-sn-glycerol (SEG), on [3H]PDBu binding to RasGRP. The competition studies with these DAGs on [3H]PDBu binding to RasGRP revealed different Ki values for these DAG molecular species. Furthermore, we transfected human Jurkat T cells by a plasmid containing RasGRP and assessed the implication of endogenous DAGs on activation of MAP kinases ERK1/ERK2, induced by phorbol-12-myristate-13-acetate (PMA). In control cells, GF109203X, a protein kinase C inhibitor, inhibited ERK1/ERK2 activation. However, this…
Age-related changes of NADPH-diaphorase-positive neurons in the rat inferior colliculus and auditory cortex
2007
Nitric oxide (NO) has been implied in age-related changes of the central nervous system (CNS) and the central auditory pathway. The present study was conducted to investigate whether the number of NO-producing cells and their morphometric characteristics in the inferior colliculus (IC) and the auditory cortex (AC) are changed with the increasing age of the subjects. IC and AC sections of adult and senile Wistar rats were studied using the histochemical detection of NADPH-diaphorase activity (NADPH-d), a marker for neurons containing nitric oxide synthase (NOS). Our results showed a decreased area of the somas of NADPH-d-positive neurons in the dorsal cortex (DC) of the IC and a diffuse loss…
Neuroproteomics in the auditory brainstem: candidate proteins for ultrafast and precise information processing.
2014
In the mammalian auditory brainstem, the cochlear nuclear complex (CN) and the superior olivary complex (SOC) feature structural and functional specializations for ultrafast (<1 ms) and precise information processing. Their proteome, the basis for structure and function, has been rarely analyzed so far. Here we identified and quantified the protein profiles of three major auditory brainstem regions of adult rats, the CN, the SOC, and the inferior colliculus (IC). The rest of the brain served as a reference. Via label-free quantitative mass spectrometry and 2-D DIGE/MALDI-MS, we identified 584 and 297 proteins in the plasma membrane/synaptic vesicle proteome and the cytosolic proteome, respe…