Search results for "complex"
showing 10 items of 5889 documents
mRNA-binding protein tristetraprolin is essential for cardiac response to iron deficiency by regulating mitochondrial function
2018
Cells respond to iron deficiency by activating iron-regulatory proteins to increase cellular iron uptake and availability. However, it is not clear how cells adapt to conditions when cellular iron uptake does not fully match iron demand. Here, we show that the mRNA-binding protein tristetraprolin (TTP) is induced by iron deficiency and degrades mRNAs of mitochondrial Fe/S-cluster-containing proteins, specifically Ndufs1 in complex I and Uqcrfs1 in complex III, to match the decrease in Fe/S-cluster availability. In the absence of TTP, Uqcrfs1 levels are not decreased in iron deficiency, resulting in nonfunctional complex III, electron leakage, and oxidative damage. Mice with deletion of Ttp …
Cytotoxic effects induced by patulin, deoxynivalenol and toxin T2 individually and in combination in hepatic cells (HepG2).
2018
Abstract Patulin (PAT), deoxynivalenol (DON) and toxin T-2 (T-2) are mycotoxins distributed worldwide in food and feed. Cytotoxicity of the three mycotoxins individually or in combination in human hepatocellular carcinoma (HepG2) cells was evaluated by MTT assay over 24, 48 and 72 h of exposure. The concentration ranges used were 0.625–15 μM for DON, 1.25–50 nM for T-2 and 0.45–7.5 μM for PAT. The IC 50 values obtained ranged from 9.30 to 2.53 μM, from 33.69 to 44.37 nM and from 2.66 to 1.17 μM for DON, T-2 and PAT, respectively. The most cytotoxic mycotoxin to HepG2 cells was T-2 followed by PAT and DON. The combination ratios used for the mixtures were 1:3 (DON: T-2), 1:5 (DON: PAT), 1:1.…
The Stalk Domain of NKp30 Contributes to Ligand Binding and Signaling of a Preassembled NKp30-CD3ζ Complex
2016
The natural cytotoxicity receptor (NCR) NKp30 (CD337) is a key player for NK cell immunosurveillance of infections and cancer. The molecular details of ligand recognition and its connection to CD3ζ signaling remain unsolved. Here, we show that the stalk domain (129KEHPQLGAGTVLLLR143) of NKp30 is very sensitive to sequence alterations, as mutations lead to impaired ligand binding and/or signaling capacity. Surprisingly, the stalk domains of NKp30 and NKp46, another NCR employing CD3ζ for signaling, were not exchangeable without drastic deficiencies in folding, plasma membrane targeting, and/or ligand-induced receptor signaling. Further mutational studies, N-glycosylation mapping, and plasma …
Enniatin B induces expression changes in the electron transport chain pathway related genes in lymphoblastic T-cell line
2018
Abstract Enniatin B is a ionophoric and lipophilic mycotoxin which reaches the bloodstream and has the ability to penetrate into cellular membranes. The purpose of this study was to reveal changes in the gene expression profile caused by enniatin B in human Jurkat lymphoblastic T-cells after 24 h of exposure at 1.5, 3 and 5 μM by next generation sequencing. It was found that up to 27% of human genome expression levels were significantly altered (5750 genes for both down-regulation and up-regulation). In the three enniatin B concentrations studied 245 differentially expressed genes were found to be overlapped, 83 were down and 162 up-regulated. ConsensusPathDB analysis of over-representation…
The Hidden Charm of Life
2019
Synthetic biology is an engineering view on biotechnology, which has revolutionized genetic engineering. The field has seen a constant development of metaphors that tend to highlight the similarities of cells with machines. I argue here that living organisms, particularly bacterial cells, are not machine-like, engineerable entities, but, instead, factory-like complex systems shaped by evolution. A change of the comparative paradigm in synthetic biology from machines to factories, from hardware to software, and from informatics to economy is discussed.
[Au(9-methylcaffein-8-ylidene) 2 ] + /DNA Tel23 System: Solution, Computational, and Biological Studies
2017
International audience; Physicochemical methods have been used to investigate interactions occurring in solution between the dicarbene gold(I) complex [Au(9‐methylcaffein‐8‐ylidene)2]BF4 (AuNHC) and a human telomeric DNA sequence, namely Tel23. Circular dichroism measurements allow identification of the conformational changes experienced by Tel23 upon interaction with AuNHC, and the respective binding stoichiometries and constants were determined. Computational studies provide a good link between previous crystallographic results of the same system and the present solution data, offering an exhaustive description of the inherent noncovalent metallodrug–DNA interactions. Remarkably, we found…
Enhanced autophagic-lysosomal activity and increased BAG3-mediated selective macroautophagy as adaptive response of neuronal cells to chronic oxidati…
2019
Oxidative stress and a disturbed cellular protein homeostasis (proteostasis) belong to the most important hallmarks of aging and of neurodegenerative disorders. The proteasomal and autophagic-lysosomal degradation pathways are key measures to maintain proteostasis. Here, we report that hippocampal cells selected for full adaptation and resistance to oxidative stress induced by hydrogen peroxide (oxidative stress-resistant cells, OxSR cells) showed a massive increase in the expression of components of the cellular autophagic-lysosomal network and a significantly higher overall autophagic activity. A comparative expression analysis revealed that distinct key regulators of autophagy are upregu…
All-atom simulations to studying metallodrugs/target interactions.
2021
Abstract Metallodrugs are extensively used to treat and diagnose distinct disease types. The unique physical–chemical properties of metal ions offer tantalizing opportunities to tailor effective scaffolds for selectively targeting specific biomolecules. Modern experimental techniques have collected a large body of structural data concerning the interactions of metallodrugs with their biomolecular targets, although being unable to exhaustively assess the molecular basis of their mechanism of action. In this scenario, the complementary use of accurate computational methods allows uncovering the minutiae of metallodrugs/targets interactions and their underlying mechanism of action at an atomic…
Analysis of Microstructure of the Cardiac Conduction System Based on Three-Dimensional Confocal Microscopy
2016
The specialised conducting tissues present in the ventricles are responsible for the fast distribution of the electrical impulse from the atrio-ventricular node to regions in the subendocardial myocardium. Characterisation of anatomical features of the specialised conducting tissues in the ventricles is highly challenging, in particular its most distal section, which is connected to the working myocardium via Purkinje-myocardial junctions. The goal of this work is to characterise the architecture of the distal section of the Purkinje network by differentiating Purkinje cells from surrounding tissue, performing a segmentation of Purkinje fibres at cellular scale, and mathematically describin…
The MRN complex is transcriptionally regulated by MYCN during neural cell proliferation to control replication stress
2015
The MRE11/RAD50/NBS1 (MRN) complex is a major sensor of DNA double strand breaks, whose role in controlling faithful DNA replication and preventing replication stress is also emerging. Inactivation of the MRN complex invariably leads to developmental and/or degenerative neuronal defects, the pathogenesis of which still remains poorly understood. In particular, NBS1 gene mutations are associated with microcephaly and strongly impaired cerebellar development, both in humans and in the mouse model. These phenotypes strikingly overlap those induced by inactivation of MYCN, an essential promoter of the expansion of neuronal stem and progenitor cells, suggesting that MYCN and the MRN complex migh…