Search results for "Cell Signaling"

Solid-Phase Synthesis and Biological Evaluation of a Teleocidin Library—Discovery of a Selective PKC Down Regulator

2000

Protein kinaseC (PKC) is linked to the signal-induced modulation of a wide variety of cellular processes, such as growth, differentiation, secretion, apoptosis, and tumor development. The design and synthesis of small molecules that regulate these different cellular signaling systems is at the forefront of modern drug design. Herein we report a) an efficient method for the synthesis of indolactamV (6), a PKC activator, and its N13-des(methyl) analogues (19) using a regioselective organometallic transformation, a convenient aminomalonate derivative (10) to introduce the appropriate functionality and an enantiospecific enzymic hydrolysis as key steps; b) the use of this method in the first so…

Quantitative characterization of tetraspanin 8 homointeractions in the plasma membrane

2021

The spatial distribution of proteins in cell membranes is crucial for signal transduction, cell communication and membrane trafficking. Members of the Tetraspanin family organize functional protein clusters within the plasma membrane into so-called Tetraspanin-enriched microdomains (TEMs). Direct interactions between Tetraspanins are believed to be important for this organization. However, studies thus far have utilized mainly co-immunoprecipitation methods that cannot distinguish between direct and indirect, through common partners, interactions. Here we study Tetraspanin 8 homointeractions in living cells via quantitative fluorescence microscopy. We demonstrate that Tetraspanin 8 exists i…

Endothelial transcriptomic changes induced by oxidized low density lipoprotein disclose an up-regulation of Jak-Stat pathway.

2015

Oxidized low density lipoproteins (oxLDLs) act as an etiological factor in the development of atherosclerosis by modifying the biological properties of endothelial cells through mechanisms of vascular inflammation. To deepen the oxLDL changes at cellular level, a transcriptomic analysis of human umbilical artery endothelial cells (HUAECs) treated with oxLDL was performed to identify the modified signaling pathways. Total RNA was isolated from HUAECs treated with oxLDL (100 μg/ml). Gene expression analysis was carried out using Affymetrix oligonucleotide microarrays. Biological pathway analysis was performed using Ingenuity Pathway Analysis software. Microarray assay demonstrated that oxLDL …

Transcriptional study after Beauvericin and Enniatin B combined exposure in Jurkat T cells

2019

Simultaneous mycotoxins toxicity is complex and non-predictable based on their individual toxicities. Beauvericin and Enniatins are emerging mycotoxins highly co-occurrent in food and feed, and their cytotoxicity has been reported in several human cell lines. RNA-seq studies of individual exposure in Jurkat cells demonstrated human genome perturbation mainly affecting mitochondrial pathways, however, both mycotoxins showed differences between their toxic responses. This study investigates the transcriptional effects of combined exposure to Beauvericin and Enniatin B (1:1) (0.1, 0.5, 1.5 μM; 24 h) in Jurkat cells by qPCR on 30 selected target genes (10 mitochondrial, 20 nuclear). Gene expres…

Chapter 7 Cell Protective Functions of Secretory Clusterin (sCLU)

2009

Secretory clusterin (sCLU) is found as an 80-kDa glycoprotein in virtually all body fluids, in serum it is associated with high-density lipoprotein (HDL). Here, we discuss demonstrated and proposed mechanisms of the cytoprotective functions of sCLU in instances of apoptosis, necrosis, and disease. These include prevention from cell damage by lipid oxidation in blood vessels, removal of dead cell remnants in tissues undergoing various forms of cell death, and clearance of harmful extracellular molecules such as amyloid beta (Aβ) by endocytosis or transcytosis. All these functions may reflect the propensity of sCLU to bind to a wide spectrum of hydrophobic molecules on one hand and to specifi…

Mind-body medicine: stress and its impact on overall health and longevity.

2005

During evolution, DNA viruses have captured a broad array of cellular genes involved in immune recognition and growth control that are nonessential for viral replication. The encoded virokines and viroceptors may act as mimetics or antagonists of their cellular homologues, altering signal transduction and cell communication towards survival of virus-infected cells. Human herpesvirus type 8 (HHV8) is the most recently identified human oncogenic herpesvirus. It is associated with Kaposi's sarcoma and lymphoproliferative diseases, such as pleural effusion lymphomas and multicentric Castleman's disease. HHV8 has captured a unique number of cellular regulatory genes, which redirect gene expressi…

New neuroprotective effect of lemon integropectin on neuronal cellular model

2021

Lemon IntegroPectin obtained via hydrodynamic cavitation of organic lemon processing waste in water shows significant neuroprotective activity in vitro, as first reported in this study investigating the effects of both lemon IntegroPectin and commercial citrus pectin on cell viability, cell morphology, reactive oxygen species (ROS) production, and mitochondria perturbation induced by treatment of neuronal SH-SY5Y human cells with H2O2. Mediated by ROS, including H2O2 and its derivatives, oxidative stress alters numerous cellular processes, such as mitochondrial regulation and cell signaling, propagating cellular injury that leads to incurable neurodegenerative diseases. These results, and t…

Bio-inorganic Nanomaterials for Biomedical Applications (Bio-silica and Polyphosphate)

2014

Bio-silica represents the main mineral component of the sponge skeletal elements (siliceous spicules), while bio-polyphosphate (polyP), a multifunctional polymer existing in microorganisms and animals, acts, among others, as reinforcement for pores in cell membranes. These natural inorganic bio-polymers, which can be readily prepared, either by recombinant enzymes (bio-silica and polyP) or chemically (polyP), are promising materials/substances for the amelioration and/or treatment of human bone diseases and dysfunctions. Bone defects in human, caused by fractures/nonunions or trauma, have an increasing impact and have become a medical challenge in the present-day aging population. Frequentl…

The cell signalling disruption theory of ageing: importance in Alzheimer’s disease and sarcopenia

2015

Should Treatment of Sepsis Include Statins?

2005

During the past decade, HMG-CoA reductase inhibitors (statins) have been shown to improve survival in patients with cardiovascular disease. Initially, the beneficial effects of statins were attributed simply to lipid reduction1; however, more recent data suggest that “pleiotropic” properties such as improvement of endothelial dysfunction, increased nitric oxide bioavailability, and antioxidative and antiinflammatory properties may contribute to the improvement of prognosis in patients with coronary artery disease. Many of these pleiotropic effects of statins are mediated by the ability to block the synthesis of important isoprenoid intermediates, which have been shown to serve as lipid atta…