Search results for "ngos"

H7, a protein kinase C inhibitor, increases the glutathione content of neuroblastoma cells

1992

AbstractIt is shown that the intracellular glutathione (GSH) concentration of neuroblastoma-2a cells in culture increases with a maximum at 24 h after starting treatment with 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H7), an inhibitor of protein kinase C (PKC). Other inhibitors of this and other protein kinases, e.g. sphingosine, staurosporine, and HA 1004, at the concentrations tested, had a less marked or negligible effect on intracellular GSH concentration. 12-O-Tetradecanoylphorbol-13-acetate (TPA) was also tested and showed no significant effect 24 h after addition.

A sphingosine kinase inhibitor combined with temozolomide induces glioblastoma cell death through accumulation of dihydrosphingosine and dihydroceram…

2014

AbstractGlioblastomas (GBMs) are very aggressive tumors with low chemosensitivity. The DNA-alkylating agent temozolomide (TMZ) is currently the most efficient chemotoxic drug for GBM therapy; however, many patients develop resistance to TMZ. Combining TMZ with another agent could present an improved treatment option if it could overcome TMZ resistance and avoid side effects. Sphingosine kinase inhibitors (SKIs) have emerged as anticancer agents. Sphingosine kinases are often overexpressed in tumors where their activity of phosphorylating sphingosine (Sph) contributes to tumor growth and migration. They control the levels of the pro-apoptotic ceramide (Cer) and Sph and of the pro-survival sp…

Cardioprotection by gene therapy

2015

Ischemic heart disease remains the leading cause of death worldwide. Ischemic pre-, post-, and remote conditionings trigger endogenous cardioprotection that renders the heart resistant to ischemic-reperfusion injury (IRI). Mimicking endogenous cardioprotection by modulating genes involved in cardioprotective signal transduction provides an opportunity to reproduce endogenous cardioprotection with better possibilities of translation into the clinical setting. Genes and signaling pathways by which conditioning maneuvers exert their effects on the heart are partially understood. This is due to the targeted approach that allowed identifying one or a few genes associated with IRI and cardioprote…

Membrane protein oxidation determines neuronal degeneration

2015

Oxidative stress is an early hallmark in neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. However, the critical biochemical effector mechanisms of oxidative neurotoxicity have remained surprisingly elusive. In screening various peroxides and potential substrates of oxidation for their effect on neuronal survival, we observed that intramembrane compounds were significantly more active than aqueous or amphiphilic compounds. To better understand this result, we synthesized a series of competitive and site-specific membrane protein oxidation inhibitors termed aminoacyllipids, whose structures were designed on the basis of amino acids frequently found at the protein-lipi…

Induction of programmed cell death in human retinoblastoma Y79 cells by C2-ceramide.

1998

C2-ceramide, a cell-permeable analogue of ceramide, induced significant, dose- and time-dependent death in human retinoblastoma Y79 cells. Dying cells strongly displayed the morphology of apoptosis as characterized by microscopic evidence of cell shrinkage, membrane blebbing, nuclear and chromatin condensation and degeneration of the nucleus into membrane-bound apoptotic bodies. Upon induction of apoptosis Y79 cells evidence early phosphatidylserine externalization, as shown by annexin V-FITC. Apoptosis was also assessed by monitoring changes in cell granularity by staining with the combined fluorescent dyes acridine orange and ethidium bromide. C2-ceramide induced these morphological chang…

Mechanism of action of sphingolipids and their metabolites in the toxicity of fumonisin B1.

2005

Fumonisins are a group of mycotoxins produced primarily by Fusarium moniliforme. Several fumonisins have been isolated through out the years but only fumonisin B1, B2 and B3 are the ones present in naturally contaminated foods, with B1 being the most toxic between them. The structural similarity between sphinganine and fumonisin B1 suggests that the mechanism of action of this mycotoxin is mainly via disruption of sphingolipid metabolism, this is an important step in the cascade of events leading to altered cell growth, differentiation and cell injury. Sphingolipids are a second type of lipid found in cell membranes, particularly nerve cells and brain tissues. Toxicity of fumonisin B1 is gi…

2020

The acid sphingomyelinase (ASM)/ceramide system exhibits a crucial role in the pathology of major depressive disorder (MDD). ASM hydrolyzes the abundant membrane lipid sphingomyelin to ceramide that regulates the clustering of membrane proteins via microdomain and lipid raft organization. Several commonly used antidepressants, such as fluoxetine, rely on the functional inhibition of ASM in terms of their antidepressive pharmacological effects. Transient receptor potential canonical 6 (TRPC6) ion channels are located in the plasma membrane of neurons and serve as receptors for hyperforin, a phytochemical constituent of the antidepressive herbal remedy St. John’s wort. TRPC6 channels are invo…

Empowering Migrant Workers and Labor NGOs in China : Creating a Law Searching Tool through a Design Science Approach

2018

Rethinking Civil Society in Development: Scales and Situated Hegemonies

2016

Ethnic residential segregation is often explained with the claim that ‘immigrants don’t want to integrate—they prefer to stick together with co-ethnics’. By contrast, mixed neighbourhoods are seen as crucial for achieving social cohesion. In line with spatial assimilation theory there is a normative assumption that people interact with those living nearby. From interviews on neighbourhood qualities and locations valued by Oslo residents of Turkish, Somali and Polish backgrounds, we raise questions about the validity of two assumptions: that most immigrants want to live in the same neighbourhoods as co-ethnics; and that they want to live close to co-ethnics because they do not want to integr…

La committenza gesuitica e la pittura a Palermo tra XVI e XVIII secolo

Il presente lavoro di ricerca mira ad approfondire e arricchire, mediante nuove acquisizioni, lo studio in merito alle opere pittoriche di committenza gesuitica custodite presso le fondazioni palermitane dell’Ordine: chiesa del Gesù a Casa Professa, Collegio Massimo dei Gesuiti, chiesa di San Stanislao Kostka e chiesa di San Francesco Saverio. A queste si aggiungono i dipinti di committenza della Compagnia trasferiti presso altre sedi. Ulteriore intento è quello di organizzare in maniera più organica la trattazione delle commissioni artistiche dell’Ordine a Palermo, che si presentava dispersiva e frammentaria. Tra i risultati più significativi si annovera il ritrovamento di un ciclo di affr…