Search results for "secret"
showing 10 items of 1132 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…
Long-chain fatty alcohols from pomace olive oil modulate the release of proinflammatory mediators
2009
Pomace olive oil is a by-product of olive oil extraction that is traditionally produced and consumed in Spain. The nonglyceride matter of this oil is a good source of interesting minor compounds, like long-chain fatty alcohols, which are present free or as part of waxes. In the present study, long-chain fatty alcohols were isolated from the nonglyceride fraction of pomace olive oil, and the composition was identified and quantified. The major components of long-chain fatty alcohols were tetracosanol, hexacosanol and octacosanol. We investigated the ability of long-chain fatty alcohols from pomace olive oil to inhibit the release of different proinflammatory mediators in vitro by cells invol…
α-Secretase Activity of the Disintegrin Metalloprotease ADAM 10: Influences of Domain Structure
2001
Disintegrin metalloproteases from different organisms form the ADAM (a disintegrin and metalloprotease) family. All members display a common domain organization and possess four potential functions: proteolysis, cell adhesion, cell fusion, and cell signaling. Members of the ADAM family are responsible for the proteolytic cleavage of transmembrane proteins and release of their extracellular domain. The proteolytic process is referred to as ectodomain shedding, which is activated by phorbol esters and inhibited by hydroxamic acid-based inhibitors. We have shown that the disintegrin metalloprotease ADAM 10 has both constitutive and regulated alpha-secretase activity. Expression of a dominant n…
Estrogen-induced cell signalling in a cellular model of Alzheimer's disease.
2003
Alzheimer's disease (AD) is characterised by deposition of a 4 kDa amyloid-beta peptide (Abeta) into senile plaques of the affected brain. Abeta is a proteolytic product of the membrane protein, amyloid precursor protein (APP). An alternative cleavage pathway involves alpha-secretase activity and results in secretion of a 100 kDa non-amyloidogenic APP (sAPPalpha) and therefore a potential reduction in Abeta secretion. We have shown that estrogen induces alpha-cleavage and therefore results in the secretion of sAPPalpha. This secretion is signalled via MAP-kinase and PI-3 kinase signal-transduction pathways. These pathways also have the potential to inhibit the activation of glycogen synthas…
Pyridinedicarboxylates, the first mechanism-derived inhibitors for prolyl 4-hydroxylase, selectively suppress cellular hydroxyprolyl biosynthesis. De…
1987
Two pyridinedicarboxylates, predicted [Hanauske-Abel (1983) M.D.-Ph.D. Thesis, Philipps Universität Marburg] and later found to be potent reversible inhibitors of purified prolyl 4-hydroxylase [Majaama, Hanauske-Abel, Günzler & Kivirikko (1984) Eur. J. Biochem. 138, 239-245] were investigated with respect to their effect on hydroxyprolyl biosynthesis in the fibroblast/collagen and the macrophage/Clq systems, and the effect was compared with that of the iron chelator 2,2′-dipyridyl, the compound usually employed to inhibit cellular hydroxyprolyl formation. Only the enzyme-mechanism-derived pyridinedicarboxylates were highly selective inhibitors, and only they lacked overt cytotoxicity. M…
Exosomes as Intercellular Signaling Organelles Involved in Health and Disease: Basic Science and Clinical Applications
2013
Cell to cell communication is essential for the coordination and proper organization of different cell types in multicellular systems. Cells exchange information through a multitude of mechanisms such as secreted growth factors and chemokines, small molecules (peptides, ions, bioactive lipids and nucleotides), cell-cell contact and the secretion of extracellular matrix components. Over the last few years, however, a considerable amount of experimental evidence has demonstrated the occurrence of a sophisticated method of cell communication based on the release of specialized membranous nano-sized vesicles termed exosomes. Exosome biogenesis involves the endosomal compartment, the multivesicu…
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.
In vivo reprogramming for tissue repair.
2015
Berninger and colleagues define milestones for in vivo reprogramming and discuss recent developments in reprogramming into pancreatic b-cells and neurons. Vital organs such as the pancreas and the brain lack the capacity for effective regeneration. To overcome this limitation, an emerging strategy consists of converting resident tissue-specific cells into the cell types that are lost due to disease by a process called in vivo lineage reprogramming. Here we discuss recent breakthroughs in regenerating pancreatic β-cells and neurons from various cell types, and highlight fundamental challenges that need to be overcome for the translation of in vivo lineage reprogramming into therapy.
Complement components C1q, C1r/C1s, and C1inh in rheumatoid arthritis
1995
Objective. To analyze the synovial site and the cell types expressing C1q, C1r/C1s, and C1–esterase inhibitor (C1INH) and to characterize newly synthesized C1q in patients with rheumatoid arthritis (RA). Methods. Tissue and primary cell cultures of synovium from RA patients were analyzed for C1q, C1r/C1s, and C1INH by Northern blotting, in situ hybridization, and pulse-chase experiments for C1q. Results. The de novo synthesis of C1q, C1r/C1s, and C1INH in synovium and primary cell cultures was proven by Northern blot and by antigenic and functional analysis. In in situ hybridization experiments, the synovial lining cell layer was identified as the site of C1q, C1r, and C1INH expression. In …
Mesadenes maturation and its hormonal control in the milkweed bug, Oncopeltus fasciatus
1993
Abstract Adult maturation of the mesadenia was examined by electron microscopy. The glandular epithelium exhibits only one cell type with a polarity along the haemocoel-lumen axis. In newly emerged males, the glands show little signs of secretory activity although the narrow lumen contains some material. Dramatic changes commence at day 2. The rER increases drastically, and at day 3 cisternae of the rER are considerably distended and include a fine granulated product. The lumen of the gland widens greatly and stores material of the same appearance as in the rER inclusions. The mode of the secretory process is not clear since membrane bound vesicles are not formed. SDS-PAGE of the secretion …