Search results for "Organ culture"
showing 10 items of 75 documents
Protective Effects of L- and D-Carnosine on R-Crystallin Amyloid Fibril Formation: Implications for Cataract Disease
2009
Mildly denaturing conditions induce bovine ?-crystallin, the major structural lens protein, to self-assemble into fibrillar structures in vitro. The natural dipeptide L-carnosine has been shown to have potential protective and therapeutic significance in many diseases. Carnosine derivatives have been proposed as potent agents for ophthalmic therapies of senile cataracts and diabetic ocular complications. Here we report the inhibitory effect induced by the peptide (L- and D-enantiomeric form) on ?-crystallin fibrillation and the almost complete restoration of the chaperone activity lost after denaturant and/or heat stress. Scanning force microscopy (SFM), thioflavin T, and a turbidimetry ass…
CD36 is involved in lycopene and lutein uptake by adipocytes and adipose tissue cultures
2011
International audience; Scope: Carotenoids are mainly stored in adipose tissue. However, nothing is known regarding the uptake of carotenoids by adipocytes. Thus, our study explored the mechanism by which lycopene and lutein, two major human plasma carotenoids, are transported. Methods and results: CD36 was a putative candidate for this uptake, 3T3-L1 cells were treated with sulfosuccinimidyl oleate, a CD36-specific inhibitor. sulfosuccinimidyl oleate-treated cells showed a significant decrease in both lycopene and lutein uptake as compared to control cells. Their uptake was also decreased by partial inhibition of CD36 expression using siRNA, whereas the overexpression of CD36 in Cos-1 cell…
Relaxant Effects of the Selective Estrogen Receptor Modulator, Bazedoxifene, and Estrogen Receptor Agonists in Isolated Rabbit Basilar Artery
2016
We have previously shown that the selective estrogen receptor modulator, bazedoxifene, improves the consequences of ischemic stroke. Now we aimed to characterize the effects and mechanisms of action of bazedoxifene in cerebral arteries. Male rabbit isolated basilar arteries were used for isometric tension recording and quantitative polymerase chain reaction. Bazedoxifene relaxed cerebral arteries, as 17-β-estradiol, 4,4',4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol [estrogen receptor (ER) α agonist], and G1 [G protein-coupled ER (GPER) agonist] did it (4,4',4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol > bazedoxifene = G1 > 17-β-estradiol). 2,3-Bis(4-hydroxyphenyl)-propionitrile (E…
Mir-4674 Regulates Angiogenesis In Tissue Injury By Targeting P38K Signaling In Endothelial Cells
2020
Neoangiogenesis is critical for tissue repair in response to injury such as myocardial ischemia or dermal wound healing. MicroRNAs are small noncoding RNAs and important regulators of angiogenesis under physiological and pathological disease states. Therefore, identification of microRNAs that may restore impaired angiogenesis in response to tissue injury may provide new targets for therapy. Using a microRNA microarray profiling approach, we identified a human-specific microRNA, miR-4674, that was significantly decreased in patients after myocardial tissue injury and had an endothelial cell (EC)-enriched expression pattern. Functionally, overexpression of miR-4674 markedly attenuated EC pro…
Inactivation of glycogen synthase kinase-3β protects against kainic acid-induced neurotoxicity in vivo
2004
Many neurodegenerative diseases involve oxidative stress and excitotoxic cell death. In an attempt to further elucidate the signal transduction pathways involved in the cell death/cell survival associated with excitotoxicity, we have used an in vivo model of excitotoxicity employing kainic acid (KA)-induced neurotoxicity. Here, we show that extracellular signal-related kinase (ERK) 2, but not ERK 1, is phosphorylated and thereby activated in the hippocampus and cerebellum of kainic acid-treated mice. Phosphorylation and hence inactivation of glycogen synthase kinase 3beta (GSK-3beta), a general survival factor, is often a downstream consequence of mitogen-activated protein kinase pathway ac…
Precision-cut liver slices: A tool to model the liver ex vivo
2013
D is ea se Precision-cut liver slices: A tool to model the liver ex vivo Peter Olinga1,2,*, Detlef Schuppan2 1Division of Pharmaceutical Technology and Biopharmacy, Departement of Pharmacy, University of Groningen, The Netherlands; 2Molecular and Translational Medicine, Department of Medicine I, University Medical Center, Johannes Gutenberg University Mainz, Germany *Corresponding author. Address: Division of Pharmaceutical Technology and Biopharmacy, Departement of Pharmacy, University of Groningen, The Netherlands. Tel.: + 31 50 363 8373; fax: +31 50 363 2500. *E-mail address: P.Olinga@rug.nl
Activity-Dependent Regulation of Neuronal Apoptosis in Neonatal Mouse Cerebral Cortex
2007
A massive neuronal loss during early postnatal development has been well documented in the murine cerebral cortex, but the factors that drive cells into apoptosis are largely unknown. The role of neuronal activity in developmental apoptosis was studied in organotypic neocortical slice cultures of newborn mice. Multielectrode array and whole-cell patch-clamp recordings revealed spontaneous network activity characterized by synchronized burst discharges, which could be blocked by tetrodotoxin and ionotropic glutamate receptor antagonists. The identical neuropharmacological manipulations also caused a significant increase in the number of apoptotic neurons as early as 6 h after the start of dr…
Tyrosine Phosphorylation Modulates the Vascular Responses of Mesenteric Arteries from Human Colorectal Tumors
2013
The aim of this study was to analyze whether tyrosine phosphorylation in tumoral arteries may modulate their vascular response. To do this, mesenteric arteries supplying blood flow to colorectal tumors or to normal intestine were obtained during surgery and prepared for isometric tension recording in an organ bath. Increasing tyrosine phosphorylation with the phosphatase inhibitor, sodium orthovanadate produced arterial contraction which was lower in tumoral than in control arteries, whereas it reduced the contraction to noradrenaline in tumoral but not in control arteries and reduced the relaxation to bradykinin in control but not in tumoral arteries. Protein expression of VEGF-A and of th…
Inhibition of different GABA transporter systems is required to attenuate epileptiform activity in the CA3 region of the immature rat hippocampus
2014
GABA transporters (GATs) are an essential element of the GABAergic system, which regulate excitability in the central nervous system and are thus used as targets for anticonvulsive therapy. However, in the immature nervous system the functions of the GABAergic system and the expression profile of GATs are distinct from the adult situation, obscuring to predict how different GAT isoforms influence epileptiform activity. Therefore we analyzed the effects of subtype specific GAT inhibitors on repetitive epileptiform discharges using field potential and whole-cell patch-clamp recordings in the CA3 region of hippocampal slices of immature (postnatal days 4-7) rats. These experiments revealed tha…
Endothelial Dysfunction in Tristetraprolin-deficient Mice Is Not Caused by Enhanced Tumor Necrosis Factor-α Expression
2014
Cardiovascular events are important co-morbidities in patients with chronic inflammatory diseases like rheumatoid arthritis. Tristetraprolin (TTP) regulates pro-inflammatory processes through mRNA destabilization and therefore TTP-deficient mice (TTP(-/-) mice) develop a chronic inflammation resembling human rheumatoid arthritis. We used this mouse model to evaluate molecular signaling pathways contributing to the enhanced atherosclerotic risk in chronic inflammatory diseases. In the aorta of TTP(-/-) mice we observed elevated mRNA expression of known TTP targets like tumor necrosis factor-α (TNF-α) and macrophage inflammatory protein-1α, as well as of other pro-atherosclerotic mediators, l…