A549 teatement with MGd
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE2189 | GEO | 2005/05/01
SECONDARY ACCESSION(S): PRJNA91247
REPOSITORIES: GEO
Similar Datasets
Project description:Human lung cancer (A549) cells were treated 50uM of the metal cation-containing chemotherapeutic drug motexafin gadolinium (MGd) for 4, 12, and 24 hrs and expression compared to control cells (treated with 5% mannitol for the same length of time)
2007-03-12 | E-GEOD-2189 | biostudies-arrayexpress
Project description:There is an emerging appreciation of the importance of zinc in regulating cancer cell growth and proliferation. Recently, we showed that the anticancer agent motexafin gadolinium (MGd) disrupted zinc metabolism in A549 lung cancer cells, leading, in the presence of exogenous zinc, to cell death. Here, we report the effect of MGd and exogenous zinc on intracellular levels of free zinc, oxidative stress, proliferation, and cell death in exponential phase human B-cell lymphoma and other hematologic cell lines. We find that increased levels of oxidative stress and intracellular free zinc precede and correlate with cell cycle arrest and apoptosis. To better understand the molecular basis of these cellular responses, gene expression profiling analyses were conducted on Ramos cell cultures treated with MGd and/or zinc acetate. Cultures treated with MGd or zinc acetate alone elicited transcriptional responses characterized by induction of metal response element-binding transcription factor-1 (MTF-1)-regulated and hypoxia-inducible transcription factor-1 (HIF-1)-regulated genes. Cultures cotreated with MGd and zinc acetate displayed further increases in the levels of MTF-1- and HIF-1-regulated transcripts as well as additional transcripts regulated by NF-E2-related transcription factor 2. These data provide insights into the molecular changes that accompany the disruption of intracellular zinc homeostasis and support a role for MGd in treatment of B-cell hematologic malignancies.
2007-10-02 | E-GEOD-2964 | biostudies-arrayexpress
Project description:We report the effect of motexafin gadolinium (MGd) and exogenous zinc on intracellular levels of free zinc, oxidative stress, proliferation, cell cycle, and cell death in exponential phase human B-cell lymphoma and other hematologic cell lines. We find that increased levels of oxidative stress and intracellular free zinc precede and correlate with cell cycle arrest and apoptotic response. Treatment with exogenous zinc increased oxidative stress and, conversely, oxidative stress resulted in increased intracellular free zinc levels. To better understand the molecular basis of these results, gene expression profiling analyses were conducted on Ramos cell cultures treated with MGd and/or zinc acetate. Cultures treated with MGd or zinc acetate alone elicited transcriptional responses characterized by induction of MTF-1 and HIF-1 regulated genes. Cultures co-treated with MGd and zinc acetate displayed further increases in the levels of MTF-1 and HIF-1 regulated transcripts as well as additional transcripts regulated by NRF-2. Overall, these studies suggest that co-treatment of Ramos cells with MGd and zinc acetate increase intracellular zinc levels with a concomitant rise in oxidative stress levels that activate adaptive survival responses but eventually lead to cell death. Keywords: Dose response
2006-01-01 | GSE2964 | GEO
Project description:Ceramides are potent influencers of cell fate and function; however, their direct molecular target(s) and mechanism of action are poorly understood. In this study, we treated primary proximal tubule epithelial cells with C2-ceramide (50uM) or its precursor C2-dihydroceramide (50uM) and used proteome integral solubility alteration (PISA) to identify potential ceramide-specific protein effectors.
2026-06-08 | PXD067617 | Pride
Project description:PrEC cells treated with either 50uM alanine or 50uM sarcosine (N-methylglycine). Gene expression is measured after 6 hours. We wish to look at the effects of sarcosine addition in relation to alanine addition. Keywords: Amino acid addition response
2009-12-31 | GSE10164 | GEO
Project description:Manipulation of zinc at the host-pathogen interface depends on both the identity of the pathogen and the nature of the host cell. In this study, we examine the response of bone marrow derived macrophages from 129S6/SvEvTac mice to infection by Salmonella Typhimurium. Unlike Balb/c and C57BL/6 mice, 129S6/SvEvTac mice possess a functional Slc11a1 (Nramp-1), a phagosomal transporter of divalent cations. We examine the changes in gene expression upon treatment with live or heat killed Salmonella at 2 Hrs and 18 Hrs post infection, and observed widespread changes in metal transport, metal-dependent, and metal homeostasis genes, suggesting significant remodeling of iron, copper, and zinc availability by host cells.
2021-02-12 | GSE166642 | GEO
Project description:In natural habitats, plants are often exposed to multiple stresses. Most studies, however, for plant abiotic stress responses analyzed those to individual stress but not combined stresses. In this report, we performed comparison analyses of gene expression to individual stresses, salt, osmotic and heat, and to a combination of these three stresses, which mimics arid conditions. We show here that the combined stress treatment induces unique gene expression pattern but not a simple reflection of the additive effects of individual stresses. First, the number of genes induced by combined stresses (150 mM NaCl, 200 mM mannitol and 35°C heat) was much smaller when compared to the sum of those induced by individual stress treatments, while the number of genes downregulated by multiple stresses was larger. A large number of genes induced by mannitol were not induced by multiple stresses, while those induced by salts were less affected in combined stress treatments. In addition, 125 genes, including13 for transcription factors, were found to be induced specifically by combined stress treatments. We report here that the plant response to a multi-stress environment represents an output of complex interactions between different stress aspects and signaling events of the various components of this environmental situation, and the determinative factor in this response is to avoid/minimize the antagonistic effects and to magnify the synergistic features of the imposed environmental challenges. Based on our results, we propose that genes that are highly induced by multiple treatments may be candidate for engineering stress tolerant crop plants. Wild-type plants of Arabidopsis thaliana were treated with three abiotic stresses, high salinity (150mM and 300mM), high osmotic pressure (200mM and 400mM mannitol) and heat (35°C), individually or simultaneously. Plants were treated with salt or mannitol for 16 hrs (first 1 hr and last 7 hrs are in light and other time in dark) or with heat for 4 hrs (in light) before sampling. There are three biologcal replicates.
2014-03-05 | E-GEOD-39956 | biostudies-arrayexpress
Project description:Molecular glue degraders (MGDs), such as pomalidomide, induce degradation of non-native substrates by the E3 ligase CRL4CRBN through its substrate receptor CRBN. To explore CRBN programmability, we tested whether reported CRBN-MGD substrates are part of a network of latent CRBN interactors, proteins capable of MGD-induced CRBN binding without detectable degradation. Leveraging highly parallel interaction measurement (GluePCA) between CRBN and zinc-fingers (ZFs), we identified ~210 ZFs bound to CRBN-pomalidomide, where top binders are already reported as degraded by dedicated MGDs. To map latent CRBN-MGD interactions proteome-wide and define the accessible CRBN interaction space, we combined AI-derived protein surface queries (MaSIF-mimicry) with GluePCA. This pipeline identified 6 known and 43 novel CRBN-pomalidomide binders, including orthogonally validated hits. We find that these binders provide privileged starting points for MGD development. We expect this binding-focused workflow to be applicable to other MGD/E3 ligase systems, potentially extending the scope of this emerging drug class.
2026-06-08 | GSE298800 | GEO
Project description:In efforts to identify additional therapeutic targets for Acute Myeloid Leukemia (AML), we performed a high-throughput screen that includes 56 primary specimens tested with 10,000 structurally diverse small molecules. One specific hit, called S656 acts as a molecular glue degrader (MGD), that mediates the CRL4-dependent proteolysis of cyclin K. Structurally, S656 features a moiety that binds to the ATP binding site of cyclin-dependent kinases (CDKs), allowing the recruitment of the CDK12-cyclin K complex, along with a binding site for DDB1 bridging the CRL4 complex. Structure activity relationship studies reveal that minimal modifications to the dimethylaniline moiety of S656 improve its cyclin K MGD function over CDK inhibition by promoting DDB1 engagement. This includes full occupation of the DDB1 pocket, preferably with hydrophobic terminal groups, and cation-π interaction with Arg928. Additionally, we demonstrate that despite structural diversity, cyclin K degraders exhibit similar functional activity in AML which is distinct from direct CDK12 inhibition.
2025-03-18 | PXD061850 | Pride
Project description:Calu-3 cells were infected with SARS-CoV2, before being treated with 50uM FG-4592 for 24 hours. The impact of cuture conditions on both the host and viral transcriptome were determined by RNA-sequencing.
2022-08-17 | GSE195870 | GEO