Search results for "binding"
showing 10 items of 3896 documents
TIMP-3 facilitates binding of target metalloproteinases to the endocytic receptor LRP-1 and promotes scavenging of MMP-1.
2020
AbstractMatrix metalloproteinases (MMPs) and the related families of disintegrin metalloproteinases (ADAMs) and ADAMs with thrombospondin repeats (ADAMTSs) play a crucial role in extracellular matrix (ECM) turnover and shedding of cell-surface molecules. The proteolytic activity of metalloproteinases is post-translationally regulated by their endogenous inhibitors, known as tissue inhibitors of metalloproteinases (TIMPs). Several MMPs, ADAMTSs and TIMPs have been reported to be endocytosed by the low-density lipoprotein receptor-related protein-1 (LRP-1). Different binding affinities of these proteins for the endocytic receptor correlate with different turnover rates which, together with di…
Down-regulation of nuclear binding activities of OXBOX-REBOX transcription factors during cellular senescence.
1996
Functional capacity of mitochondria declines during aging and this impairment may have a major role in aging process. Several observations indicate that transcriptional efficiency is reduced during aging. Our purpose was to find out whether aging and cellular senescence affect the nuclear binding activities of transcription factors which bind to OXBOX-REBOX sequence present in promoter regions of numerous nuclear genes encoding mitochondrial proteins. These factors regulate and coordinate the expression of mitochondrial proteins. We observed a strong down-regulation in the nuclear binding activities of OXBOX-REBOX factors in replicatively senesced human WI-38 and IMR-90 fibroblasts. On the …
Vitamin E transport, membrane incorporation and cell metabolism: Is α-tocopherol in lipid rafts an oar in the lifeboat?
2010
International audience; Vitamin E is composed of closely related compounds, including tocopherols and tocotrienols. Studies of the last decade provide strong support for a specific role of alpha-tocopherol in cell signalling and the regulation of gene expression. It produces significant effects on inflammation, cell proliferation and apoptosis that are not shared by other vitamin E isomers with similar antioxidant properties. The different behaviours of vitamin E isomers might relate, at least in part, to the specific effects they exert at the plasma membrane. alpha-Tocopherol is not randomly distributed throughout the phospholipid bilayer of biological membranes, and as compared with other…
Selectivity of pharmacological tools: implications for use in cell physiology. A Review in the Theme: Cell Signaling: Proteins, Pathways and Mechanis…
2014
Pharmacological inhibitors are frequently used to identify the receptors, receptor subtypes, and associated signaling pathways involved in physiological cell responses. Based on the effects of such inhibitors conclusions are drawn about the involvement of their assumed target or lack thereof. While such inhibitors can be useful tools for a better physiological understanding, their uncritical use can lead to incorrect conclusions. This article reviews the concept of inhibitor selectivity and its implication for cell physiology. Specifically, we discuss the implications of using inhibitor vs. activator approaches, issues of direct vs. indirect pathway modulation, implications of inverse agoni…
Odorant binding changes the electrical properties of olfactory receptors at the nanoscale
2021
Olfactory receptors (ORs) comprise the largest multigene family in the vertebrates. They belong to the class A (rhodopsin-like) family of G protein-coupled receptors (GPCRs), which are the most abundant membrane proteins, having widespread, significant roles in signal transduction in cells, and therefore, they are a major pharmacological target. Moreover, ORs displayed high selectivity and sensitivity towards odorant detection, a characteristic that raised the interest for developing biohybrid sensors based on ORs for the detection of volatile compounds. The transduction of odorant binding into cellular signaling by ORs is not well understood and knowing its mechanism would enable developin…
A specific CD4 epitope bound by tregalizumab mediates activation of regulatory T cells by a unique signaling pathway
2014
CD4(+)CD25(+) regulatory T cells (Tregs) represent a specialized subpopulation of T cells, which are essential for maintaining peripheral tolerance and preventing autoimmunity. The immunomodulatory effects of Tregs depend on their activation status. Here we show that, in contrast to conventional anti-CD4 monoclonal antibodies (mAbs), the humanized CD4-specific monoclonal antibody tregalizumab (BT-061) is able to selectively activate the suppressive properties of Tregs in vitro. BT-061 activates Tregs by binding to CD4 and activation of signaling downstream pathways. The specific functionality of BT-061 may be explained by the recognition of a unique, conformational epitope on domain 2 of th…
Computational identification of cell-specific variable regions in ChIP-seq data.
2019
ABSTRACT Chromatin immunoprecipitation followed by sequencing (ChIP-seq) is used to identify genome-wide DNA regions bound by proteins. Several sources of variation can affect the reproducibility of a particular ChIP-seq assay, which can lead to a misinterpretation of where the protein under investigation binds to the genome in a particular cell type. Given one ChIP-seq experiment with replicates, binding sites not observed in all the replicates will usually be interpreted as noise and discarded. However, the recent discovery of high-occupancy target (HOT) regions suggests that there are regions where binding of multiple transcription factors can be identified. To investigate these regions,…
Loss of input from the mossy cells blocks maturation of newly generated granule cells.
2007
The objective of this work is to check whether the input from the mossy cells to the inner molecular layer is necessary for the integration and maturation of the newly generated granule cells of the dentate gyrus (DG) in mice, and if after status epilepticus the sprouting of the mossy fibers can substitute for this projection. Newly generated cells were labeled by administration of 5-bromo-deoxyuridine either before or after pilocarpine administration. The neuronal loss in the hippocampus after administration of pilocarpine combined with scopolamine and diazepam seemed restricted to the hilar mossy cells. The maturation of the granule cells was studied using immunohistochemistry for calreti…
Identification and characterization of the nano-sized vesicles released by muscle cells
2013
AbstractSeveral cell types secrete small membranous vesicles that contain cell-specific collections of proteins, lipids, and genetic material. The function of these vesicles is to allow cell-to-cell signaling and the horizontal transfer of their cargo molecules. Here, we demonstrate that muscle cells secrete nano-sized vesicles and that their release increases during muscle differentiation. Analysis of these nanovesicles allowed us to characterize them as exosome-like particles and to define the potential role of the multifunctional protein Alix in their biogenesis.
MOLECULAR BASIS OF DRUG PHOTOTOXICITY: PHOTOSENSITIZED CELL DAMAGE BY THE MAJOR PHOTOPRODUCT OF TIAPROFENIC ACID
1994
Tiaprofenic acid is a photosensitizing nonsteroidal anti-inflammatory drug, whose major photoproduct (decarboxytiaprofenic acid) is also a potent photosensitizer. Because of the lack of the carboxylate moiety, this photoproduct is more lipophilic and might bind more efficiently to cell membranes, thereby causing phototoxic damage. To verify the feasibility of this hypothesis, we have prepared the 3H-labeled analogs of tiaprofenic acid and its photoproduct and examined the binding, persistence and phototoxicity of the photoproduct using poorly metabolizing (fibroblasts) and actively metabolizing cells (hepatocytes). The photoproduct of tiaprofenic acid accumulates in both cell types as it is…