Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA264091 | ENA |
REPOSITORIES: ENA
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Project description:We have previously demonstrated that molecular hydrogen (H2) neutralizes hydroxyl radical (M-bM-^@M-"OH) in cultured-cells and protects cells and tissues against oxidative stress. Growing evidence has confirmed that H2-consumption exhibits preventive and therapeutic effects in patients with various diseases as well as model animals. Moreover, a small amount of H2 modulates signal transduction for regulating the expression of various genes; however, the primary target of H2 for exhibiting a variety of phenotypes was completely unknown. Here we show that H2 at low amounts manipulates oxidized phospholipid mediators to modulate Ca2+-signal transduction and gene expression. Gene expression was measured at 4 hours after exposure to phospholipid, PAPC or oxidized PAPC that had been air-oxidized for 3 days with 0, 1.3 or 5% H2. Three independent experiments were performed for each experiment.
2014-10-17 | E-GEOD-62434 | biostudies-arrayexpress
Project description:We have previously demonstrated that molecular hydrogen (H2) neutralizes hydroxyl radical (•OH) in cultured-cells and protects cells and tissues against oxidative stress. Growing evidence has confirmed that H2-consumption exhibits preventive and therapeutic effects in patients with various diseases as well as model animals. Moreover, a small amount of H2 modulates signal transduction for regulating the expression of various genes; however, the primary target of H2 for exhibiting a variety of phenotypes was completely unknown. Here we show that H2 at low amounts manipulates oxidized phospholipid mediators to modulate Ca2+-signal transduction and gene expression.
2014-10-17 | GSE62434 | GEO
Project description:Our hypothesis is that copper modulates the activity of multiple intracellular signal transduction pathways to affect transcription. We have previously shown that copper activates transcription through both metal- and oxidative stress-responsive signal transduction pathways. Since the global molecular mechanisms underlying copper toxicity have not been well elucidated in humans, we have profiled transcriptome changes in HepG2 cells exposed to 100, 200, 400 and 600 uM copper for 4, 8, 12 and 24 hours using a human oligonucleotide microarray. Differentially expressed genes were identified, and integrated into biological and functional pathways through Gene Ontology analysis. Global gene expression profile was overlaid onto biomolecular interaction networks and signal transduction cascades using pathway mapping and interactome identification. Keywords: copper toxicity, HepG2 cells, copper concentrations: 100, 200, 400 and 600 uM, exposure times: 4, 8, 12, and 24 h, expression profiles of copper-responsive genes
2009-06-25 | GSE9539 | GEO
Project description:Extracellular superoxide dismutase (SOD3), which dismutases hydrogen peroxide to superoxide anion at cell membranes, mimics RAS oncogene action inducing primary cell immortalization at sustained low-level expression while high expression activates cancer barrier signaling through p53-p21 growth arrest pathway. We have previously demonstrated that the growth regulation of SOD3 occurs at the level of RAS and is mediated through non-transcriptional and transcriptional routes. Therefore, in the current work we assayed the growth suppressive mechanisms of SOD3 by characterizing the main signal transduction routes from the cell membrane into the nucleus. Based on our data robust over-expression of SOD3 in anaplastic thyroid cancer 8505c cells increased EGFR, RYK, ALK, FLT3, and EPHA10 tyrosine kinase receptor phosphorylation with consequent downstream SRC, FYN, YES, HCK, and LYN kinase activation. However, RAS pull-down experiment suggested lack of mitogen pathway stimulation that was confirmed by MEK1/2 and ERK1/2 Western blot. Interestingly, mRNA expression analysis indicated that SOD3 regulated in a dose dependent manner the expression of selected guanine nucleotide exchange factors (Rho GEF16, Ral GEF RGL1), GTPase activating proteins (ArfGAP ADAP2, Ras GAP RASAL1, RGS4), and Rho guanine nucleotide disassociation inhibitors (Rho GDI 2) therefore controlling the signal transduction through RAS GTPases to downstream signal transduction pathways. Our current data suggests a SOD3-induced activation of growth signal transduction is controlled in a dose dependent manner through GEF, GAP, and GDI.
2014-12-31 | GSE56546 | GEO
Project description:Ras/cAMP signal transduction, perturbations
| PRJNA92621 | ENA
Project description:Ultraviolet light is the dominant environmental oxidative skin stressor and a major skin aging factor. We studied which oxidized phospholipid (OxPL) mediators Ultraviolet A (UVA) would generate in primary human keratinocytes (KC). Mass spectrometric analysis of the oxidized phospholipidome of KC immediately or 24h post stress revealed dynamic changes in abundance of 174 oxidized phosphocholine species. Exposure to UVA and to in vitro UVA - oxidized phospholipids both activated, on transcriptome and proteome level, NRF2/antioxidant response signaling and lipid metabolizing enzyme expression, whereas UVA additionally initiated the unfolded protein response (UPR). We identified Nupr1 as an upstream transcriptional regulator of UVA/OxPL mediated gene expression that is itself transcriptionally regulated by reactive lipids, which also aggregate and crosslink recombinant Nupr1 protein. Nupr1 governs the basal and stress regulated expression of cell cycle, redox reactive, autophagy- and lipid metabolizing genes in epidermal keratinocytes, making it a potential key factor in skin ROS responses, -aging and -pathology.
2019-05-27 | PXD008050 | Pride
Project description:The mechanisms by which the epidermis responds to disturbances in barrier function and restores homeostasis are unknown. With a disruption of the epidermal barrier, water is lost resulting in an increase in extracellular sodium concentration. We demonstrate that the sodium channel Nax functions as the sodium sensor. With increased extracellular sodium, Nax up-regulates prostasin which results in activation of the sodium channel ENaC, resulting in increased sodium flux and increased downstream mRNA synthesis of inflammatory mediators. The same pathways are present in lung epithelial cells. A signal transduction pathway mediated directly through Nax and secondarily through ENaC results in production of secretory inflammatory mediators. These mediators result in epithelial proliferation and restoration of epidermal homeostasis, but can also have negative effects including excess inflammation and ultimately leads to activation of fibroblasts.
2015-01-29 | GSE65366 | GEO
Project description:Infection by the human pathogenic fungus Aspergillus fumigatus is initialized by the outgrowth of asexual spores (conidia) into the lung tissue of the immunocompromised host following an inhalation of the airborne conidia. The resident phagocytes, the alveolar macrophages are the first immune cells to encounter invading conidia. However, A. fumigatus conidia employ versatile mechanisms to evade the host immune defense and establish a severe invasive infection. Previously, we showed that depending on the presence of conidial 1,8-dihydroxynaphthalene (DHN) melanin, A. fumigatus circumvents intracellular killing by manipulating the phagolysosomal maturation process. Here, by comparative dual proteomics we analyzed proteins of phagolysosomes containing melanized wild-type or non-melanized pksP mutant conidia. Bioinformatics compiled a regulatory module of differentially abundant proteins that mirrors processes targeted by the fungus for immune evasion. Those are i.e. vATPAse-driven phagolysosomal acidification, endocytic trafficking, signal transduction, energy metabolism and immune response. In detail, we found alterations of vATPase complex assembly and impaired abundances of mTOR and MAPK signaling molecules, Rab5 and Vamp8 mediators of endosomal trafficking as well as Lamp1 and cathepsin Z lysosomal markers.
2018-03-08 | PXD006134 | Pride
Project description:Excessive levels of reactive oxygen species (ROS) cause cellular stress through damage to all classes of macromolecules and result in cell death. However, ROS can also act as signaling molecules in various biological processes. In plants, ROS signaling has been documented in environmental stress perception, plant development and cell death amongst others. Knowledge on the regulatory events governing ROS signal transduction is however still scratching the surface. To further elucidate the transcriptional response and regulation upon ROS accumulation we supplemented Arabidopsis seedlings with a 10mM hydrogen peroxide (H2O2) solution to trigger oxidative stress.
2016-06-10 | GSE80200 | GEO
Project description:Human SZ95 sebocytes were transfected by lipofection with either scramble siRNA or OLR1 siRNA and after 24h were treated with 25µg/ml of UV-oxidized 1-palmitoyl-2-arachidonoyl-sn-phosphocholine (UVPAPC) for 7 hours. Phospholipid oxidation products (OxPL) are versatile stress signaling mediators in the skin. These lipid signaling molecules can be generated non-enzymatically or enzymatically by ultraviolet light, the major extrinsic skin aging factor. OxPL regulate cytoprotective, immunological and metabolic adaptation of the skin to oxidant stress. We here investigated whether the scavenger receptor Oxidized Low Density Lipoprotein Receptor 1 (OLR1, LOX-1) would have a function in cutaneous oxPL signaling. We found that OLR1 is expressed in several cutaneous cell types, most prominently in cells of the sebaceous gland and in keratinocytes. We repressed OLR1 expression with siRNA in SZ95 sebocytes, exposed cells to oxidized 1-palmitoyl-2-arachidonoyl-sn-phosphatiylcholine (PAPC) and performed transcriptomic profiling. Bioinformatic analysis revealed that OxPL exposure induced the Nrf2 antioxidant stress response and aldosterone signaling. The analysis also revealed that OLR1 is not required for the transcriptional regulation induced by oxidized PAPC, but interestingly, OLR1 knockdown affected expression of CNN2, HMRR, ITGB6 and KIF20A, all genes governing cell proliferation and motility. We identify sebocytes as cutaneous cells responsive to lipid mediated redox stress which is not dependent on the scavenger receptor OLR1.
2020-04-15 | GSE98335 | GEO