Search results for "Acellular"
showing 10 items of 1986 documents
Inhibitors of Rho-kinase modulate amyloid-β (Aβ) secretion but lack selectivity for Aβ42
2005
Certain non-steroidal anti-inflammatory drugs (NSAIDs) preferentially inhibit production of the amyloidogenic Abeta42 peptide, presumably by direct modulation of gamma-secretase activity. A recent report indicated that NSAIDs could reduce Abeta42 by inhibition of the small GTPase Rho, and a single inhibitor of Rho kinase (ROCK) mimicked the effects of Abeta42-lowering NSAIDs. To investigate whether Abeta42 reduction is a common property of ROCK inhibitors, we tested commercially available compounds in cell lines that were previously used to demonstrate the Abeta42-lowering activity of NSAIDs. Surprisingly, we found that two ROCK inhibitors reduced total Abeta secretion in a dose-dependent m…
Neuronal cell cultures: A tool for investigations in developmental neurobiology
1992
The aim of this review is to describe environmental requirements for survival of neuronal cells in culture, and secondly to survey the complex interplay between hormones, neurotrophic factors, transport- and extracellular matrix- proteins, which characterize the developmental program of differentiating neurons. An overall reconsideration of the literature in this vast field is above the limits of the present paper; since progress and refinement in the techniques of neuronal cell cultures have paralleled the advancement in Developmental Neurobiology, we will run instead through the main steps which form the conceptual framework of neuronal cell cultures. © 1992 Plenum Publishing Corporation.
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…
Regulated segregation of kinase Dyrk1A during asymmetric neural stem cell division is critical for EGFR-mediated biased signaling.
2010
SummaryStem cell division can result in two sibling cells exhibiting differential mitogenic and self-renewing potential. Here, we present evidence that the dual-specificity kinase Dyrk1A is part of a molecular pathway involved in the regulation of biased epidermal growth factor receptor (EGFR) signaling in the progeny of dividing neural stem cells (NSC) of the adult subependymal zone (SEZ). We show that EGFR asymmetry requires regulated sorting and that a normal Dyrk1a dosage is required to sustain EGFR in the two daughters of a symmetrically dividing progenitor. Dyrk1A is symmetrically or asymmetrically distributed during mitosis, and biochemical analyses indicate that it prevents endocyto…
Shed membrane vesicles and clustering of membrane-bound proteolytic enzymes
2003
Publisher Summary Eukaryotic cells appear to release into the extracellular medium several populations of exovesicles, which are suggested to have different origins and functions and are identified by different names. This chapter deals with vesicles believed to originate from the cell membrane and named membrane vesicles. These are structures in which membrane-bound proteolytic enzymes are clustered and they play important roles in matrix remodeling. Relatively large membrane vesicles (diameters ranging from 100 nm to 1 μm) are shed from plasma membranes through unidentified budding mechanisms. These membrane structures are enriched in selected plasma-membrane components including integrin…
Characterization of the Receptor Protein-Tyrosine Kinase Gene from the Marine Sponge Geodia cydonium
1996
Cells are provided with well-defined receptor structures (signal receivers) which interact with their corresponding ligands (signal molecules) and initiate a signal transduction pathway resulting in a change of cellular behavior or metabolism (Stoddard et al. 1992). It is well established that cells from both eukaryotic protists (single-cell organisms) and from Metazoa (multicellular organisms) respond to signals emanating from the extracellular environment. The extracellular signals to which protists respond are mainly nutrients which diffuse to their surfaces, and in most cases cross the cell membrane. In addition, they are able to bind peptide hormones, e.g., insulin or adrenocorticotrop…
Concentration-dependent T cell activation by different types of proteins
2009
We investigated the concentration-dependent stimulation of T cells by different human proteins. Quantitative changes in the extent of activation, as well as qualitative changes within the type of activation, were measured. At low, physiological concentrations of extracellular human proteins (0.2 µg/ml), CD4 and CD8 T lymphocytes were suppressed. In contrast, at high protein concentrations (2 mg/ml), CD4 T cells were suppressed, but we also observed a concurrent increase in the level of CD8 T cell activation. Our results are consistent with the phenomenon of cross-presentation, whereby the addition of intracellular proteins leads to the activation of both CD4 and CD8 T cells. Further additio…
Human Hsp10 and Early Pregnancy Factor (EPF) and their relationship and involvement in cancer and immunity: current knowledge and perspectives.
2009
This article is about Hsp10 and its intracellular and extracellular forms focusing on the relationship of the latter with Early Pregnancy Factor and on their roles in cancer and immunity. Cellular physiology and survival are finely regulated and depend on the correct functioning of the entire set of proteins. Misfolded or unfolded proteins can cause deleterious effects and even cell death. The chaperonins Hsp10 and Hsp60 act together inside the mitochondria to assist protein folding. Recent studies demonstrated that these proteins have other roles inside and outside the cell, either together or independently of each other. For example, Hsp10 was found increased in the cytosol of different t…
The Functional Role of the Second NPXY Motif of the LRP1 β-Chain in Tissue-type Plasminogen Activator-mediated Activation of N-Methyl-D-aspartate Rec…
2008
The low density lipoprotein receptor-related protein 1 (LRP1) emerges to play fundamental roles in cellular signaling pathways in the brain. One of its prominent ligands is the serine proteinase tissue-type plasminogen activator (tPA), which has been shown to act as a key activator of neuronal mitogen-activated protein kinase pathways via the N-methyl-D-aspartate (NMDA) receptor. However, here we set out to examine whether LRP1 and the NMDA receptor might eventually act in a combined fashion to mediate tPA downstream signaling. By blocking tPA from binding to LRP1 using the receptor-associated protein, we were able to completely inhibit NMDA receptor activation. Additionally, inhibition of …
An unconventional role for miRNA: let-7 activates Toll-like receptor 7 and causes neurodegeneration
2011
Activation of innate immune receptors by host-derived factors exacerbates CNS damage, but the identity of these factors remains elusive. We uncovered an unconventional role for the microRNA let-7, a highly abundant regulator of gene expression in the CNS, in which extracellular let-7 activates the RNA-sensing Toll-like receptor (TLR) 7 and induces neurodegeneration through neuronal TLR7. Cerebrospinal fluid (CSF) from individuals with Alzheimer’s disease contains increased amounts of let-7b, and extracellular introduction of let-7b into the CSF of wild-type mice by intrathecal injection resulted in neurodegeneration. Mice lacking TLR7 were resistant to this neurodegenerative effect, but thi…