Search results for "B1"
showing 10 items of 1109 documents
In vivo effects of tumor necrosis factor-α or flavone acetic acid in combination with doxorubicin on multidrug-resistant B16 melanoma
1996
Having observed that tumor necrosis factor (TNF)-alpha and doxorubicin (DXR) produce a synergistic inhibition of melanoma B16 and also of its multidrug resistant (MDR) variant in vitro, we tested whether this interaction would occur in vivo as well. C57BL/6 mice with s.c. tumors were treated with TNF or flavone acetic acid (FAA), a biological response modifier, in simultaneous or sequential combination with DXR. The agents were administered systemically. Overall, the results were negative, apart from a trend towards slight synergy, found in the chemosensitive melanoma, when TNF was given 1 or 2 days before DXR. The effects of FAA and DXR were found to be subadditive or antagonistic. However…
New insight into the genetics of age-related macular degeneration in connection with lipid metabolism
2010
Evaluation of: Zerbib J, Seddon JM, Richard F et al. rs5888 variant of SCARB1 gene is a possible susceptibility factor for age-related macular degeneration. PLoS ONE 4(10), e7341 (2009).Age-related macular degeneration (AMD) is the leading cause of visual loss in elderly populations of Western countries. According to demographic forecasts, and owing to the improvement in life expectancy, the number of people suffering from this pathology is expected to dramatically increase in the near future, thereby becoming a significant socioeconomic burden. There has been great progress in defining risk factors for AMD over the last few decades. Beyond advanced age, environmental and genetic factors ha…
Anti-inflammatory lipoxin A4 is an endogenous allosteric enhancer of CB1 cannabinoid receptor.
2012
Allosteric modulation of G-protein–coupled receptors represents a key goal of current pharmacology. In particular, endogenous allosteric modulators might represent important targets of interventions aimed at maximizing therapeutic efficacy and reducing side effects of drugs. Here we show that the anti-inflammatory lipid lipoxin A 4 is an endogenous allosteric enhancer of the CB 1 cannabinoid receptor. Lipoxin A 4 was detected in brain tissues, did not compete for the orthosteric binding site of the CB 1 receptor (vs. 3 H-SR141716A), and did not alter endocannabinoid metabolism (as opposed to URB597 and MAFP), but it enhanced affinity of anandamide at the CB1 receptor, thereby potentiating …
The complex modulation of lysosomal degradation pathways by cannabinoid receptors 1 and 2
2015
The two main receptors of the endocannabinoid system, cannabinoid receptors 1 (CB1R) and 2 (CB2R), were described in the early 1990s. Since then, different physiological functions have been revealed that are linked to the activity of these two G-protein-coupled receptors. CB1R and CB2R activities influence signal cascades, which are known to play a role in the regulation of the cellular "self-digestion" process called autophagy. A variety of these signaling pathways are integrated by the mammalian target of rapamycin complex 1 (mTORC1) that acts as an inhibitor of autophagy. Others, like AMP-activated protein kinase dependent signaling pathway, are able to bypass mTORC1 to modulate the auto…
The Endocannabinoid System Promotes Astroglial Differentiation by Acting on Neural Progenitor Cells
2006
Endocannabinoids exert an important neuromodulatory role via presynaptic cannabinoid CB1receptors and may also participate in the control of neural cell death and survival. The function of the endocannabinoid system has been extensively studied in differentiated neurons, but its potential role in neural progenitor cells remains to be elucidated. Here we show that the CB1receptor and the endocannabinoid-inactivating enzyme fatty acid amide hydrolase are expressed, bothin vitroandin vivo, in postnatal radial glia (RC2+cells) and in adult nestin type I (nestin+GFAP+) neural progenitor cells. Cell culture experiments show that CB1receptor activation increases progenitor proliferation and differ…
The endocannabinoid N-arachidonoyldopamine (NADA) exerts neuroprotective effects after excitotoxic neuronal damage via cannabinoid receptor 1 (CB(1)).
2012
Endocannabinoids exert numerous effects in the CNS under physiological and pathological conditions. The aim of the present study was to examine whether the endocannabinoid N-arachidonoyldopamine (NADA) may protect neurons in excitotoxically lesioned organotypic hippocampal slice cultures (OHSC). OHSC were excitotoxically lesioned by application of N-methyl-d-aspartate (NMDA, 50 μM) for 4 h and subsequently treated with different NADA concentrations (0.1 pM-50 μM) alone or in combination with cannabinoid receptor antagonists. NADA protected dentate gyrus granule cells and caused a slight reduction in the number of microglial cells. The number of degenerated neurons significantly decreased be…
Cannabinoid CB1 receptors regulate neuronal TNF-α effects in experimental autoimmune encephalomyelitis.
2011
Abstract Cannabinoid CB1 receptors (CB1Rs) regulate the neurodegenerative damage of experimental autoimmune encephalomyelitis (EAE) and of multiple sclerosis (MS). The mechanism by which CB1R stimulation exerts protective effects is still unclear. Here we show that pharmacological activation of CB1Rs dampens the tumor necrosis factor α (TNFα)-mediated potentiation of striatal spontaneous glutamate-mediated excitatory postsynaptic currents (EPSCs), which is believed to cogently contribute to the inflammation-induced neurodegenerative damage observed in EAE mice. Furthermore, mice lacking CB1Rs showed a more severe clinical course and, in parallel, exacerbated alterations of sEPSC duration af…
Subsynaptic Distribution, Lipid Raft Targeting and G Protein-Dependent Signalling of the Type 1 Cannabinoid Receptor in Synaptosomes from the Mouse H…
2021
Numerous studies have investigated the roles of the type 1 cannabinoid receptor (CB1) in glutamatergic and GABAergic neurons. Here, we used the cell-type-specific CB1 rescue model in mice to gain insight into the organizational principles of plasma membrane targeting and Gαi/o protein signalling of the CB1 receptor at excitatory and inhibitory terminals of the frontal cortex and hippocampus. By applying biochemical fractionation techniques and Western blot analyses to synaptosomal membranes, we explored the subsynaptic distribution (pre-, post-, and extra-synaptic) and CB1 receptor compartmentalization into lipid and non-lipid raft plasma membrane microdomains and the signalling properties.…
Neuron-type specific cannabinoid-mediated G protein signalling in mouse hippocampus
2013
Type 1 cannabinoid receptor (CB1) is expressed in different neuronal populations in the mammalian brain. In particular, CB1 on GABAergic or glutamatergic neurons exerts different functions and display different pharmacological properties in vivo. This suggests the existence of neuron-type specific signalling pathways activated by different subpopulations of CB1. In this study, we analysed CB1 expression, binding and signalling in the hippocampus of conditional mutant mice, bearing CB1 deletion in GABAergic (GABA-CB1-KO mice) or cortical glutamatergic neurons (Glu-CB1-KO mice). Compared to their wild-type littermates, Glu-CB1-KO displayed a small decrease of CB1 mRNA amount, immunoreactivity…
WIN55,212-2-induced expression of Mir-29b1 favours the suppression of osteosarcoma cell migration in a SPARC-independent manner
2019
WIN55,212-2 (WIN) is a synthetic agonist of cannabinoid receptors that displays promising antitumour properties. The aim of this study is to demonstrate that WIN is able to block the migratory ability of osteosarcoma cells and characterize the mechanisms involved. Using wound healing assay and zymography, we showed that WIN affects cell migration and reduces the activity of the metalloproteases MMP2 and MMP9. This effect seemed to be independent of secreted protein acidic and rich in cysteine (SPARC), a matricellular protein involved in tissue remodeling and extracellular matrix deposition. SPARC release was indeed prevented by WIN, and SPARC silencing by RNA interference did not influence …