Latest o news

Certain ortho-hydroxylated brominated ethers are promiscuous kinase inhibitors that impair neuronal signaling and neurodevelopmental processes [Cell Biology]

By feedproxy.google.com
Published On :: 2020-05-01T00:06:09-07:00

The developing nervous system is remarkably sensitive to environmental signals, including disruptive toxins, such as polybrominated diphenyl ethers (PBDEs). PBDEs are an environmentally pervasive class of brominated flame retardants whose neurodevelopmental toxicity mechanisms remain largely unclear. Using dissociated cortical neurons from embryonic Rattus norvegicus, we found here that chronic exposure to 6-OH–BDE-47, one of the most prevalent hydroxylated PBDE metabolites, suppresses both spontaneous and evoked neuronal electrical activity. On the basis of our previous work on mitogen-activated protein kinase (MAPK)/extracellular signal-related kinase (ERK) (MEK) biology and our observation that 6-OH–BDE-47 is structurally similar to kinase inhibitors, we hypothesized that certain hydroxylated PBDEs mediate neurotoxicity, at least in part, by impairing the MEK–ERK axis of MAPK signal transduction. We tested this hypothesis on three experimental platforms: 1) in silico, where modeling ligand–protein docking suggested that 6-OH–BDE-47 is a promiscuous ATP-competitive kinase inhibitor; 2) in vitro in dissociated neurons, where 6-OH–BDE-47 and another specific hydroxylated BDE metabolite similarly impaired phosphorylation of MEK/ERK1/2 and activity-induced transcription of a neuronal immediate early gene; and 3) in vivo in Drosophila melanogaster, where developmental exposures to 6-OH–BDE-47 and a MAPK inhibitor resulted in offspring displaying similarly increased frequency of mushroom-body β–lobe midline crossing, a metric of axonal guidance. Taken together, our results support that certain ortho-hydroxylated PBDE metabolites are promiscuous kinase inhibitors and can cause disruptions of critical neurodevelopmental processes, including neuronal electrical activity, pre-synaptic functions, MEK–ERK signaling, and axonal guidance.

Certain ortho-hydroxylated brominated ethers are promiscuous kinase inhibitors that impair neuronal signaling and neurodevelopmental processes [Cell Biology]

The testis-specific LINC component SUN3 is essential for sperm head shaping during mouse spermiogenesis [Cell Biology]

WYSIWYG Web Builder 7.5 available now!

WYSIWYG Web Builder 8.5 available now!

Genetic Profile and Functional Proteomics of Anal Squamous Cell Carcinoma: Proposal for a Molecular Classification

A Quantitative Tri-fluorescent Yeast Two-hybrid System: From Flow Cytometry to In cellula Affinities

Phenotypic Adaption of Pseudomonas aeruginosa by Hacking Siderophores Produced by Other Microorganisms

Tandem Mass Tag Approach Utilizing Pervanadate BOOST Channels Delivers Deeper Quantitative Characterization of the Tyrosine Phosphoproteome

Integrative Metabolic Pathway Analysis Reveals Novel Therapeutic Targets in Osteoarthritis

Organellar maps through proteomic profiling - a conceptual guide

Peptide-based interaction proteomics

The DNA sensor cGAS is decorated by acetylation and phosphorylation modifications in the context of immune signaling

Modulation of natural HLA-B*27:05 ligandome by ankylosing spondylitis-associated endoplasmic reticulum aminopeptidase 2 (ERAP2)

HIGD2A is required for assembly of the COX3 module of human mitochondrial complex IV

Chemical Genetics of AGC-kinases Reveals Shared Targets of Ypk1, Protein Kinase A and Sch9

Characterization of Prenylated C-terminal Peptides Using a Thiopropyl-based Capture Technique and LC-MS/MS

Flow-induced reorganization of laminin-integrin networks within the endothelial basement membrane uncovered by proteomics

Seminal Plasma Proteome as an Indicator of Sperm Dysfunction and Low Sperm Motility

Cell Cycle Profiling Reveals Protein Oscillation, Phosphorylation, and Localization Dynamics

Proteaphagy in mammalian cells can function independent of ATG5/ATG7

Robust summarization and inference in proteome-wide label-free quantification

Investigation of inter- and intra-tumoral heterogeneity of glioblastoma using TOF-SIMS

Dysregulation of Exosome Cargo by Mutant Tau Expressed in Human-Induced Pluripotent Stem Cell (iPSC) Neurons Revealed by Proteomics Analyses

Developments and Applications of Functional Protein Microarrays

Identification of an Unconventional Subpeptidome Bound to the Behcet's Disease-associated HLA-B*51:01 that is Regulated by Endoplasmic Reticulum Aminopeptidase 1 (ERAP1)

Human Hepatocyte Nuclear Factor 4-{alpha} Encodes Isoforms with Distinct Transcriptional Functions

Quantitative proteomics of human heart samples collected in vivo reveal the remodeled protein landscape of dilated left atrium without atrial fibrillation

Arginine in C9ORF72 Dipolypeptides Mediates Promiscuous Proteome Binding and Multiple Modes of Toxicity

Immediate adaptation analysis implicates BCL6 as an EGFR-TKI combination therapy target in NSCLC

A cross-linking mass spectrometry approach defines protein interactions in yeast mitochondria

Characterization of signaling pathways associated with pancreatic {beta}-cell adaptive flexibility in compensation of obesity-linked diabetes in db/db mice

The Data Must Be Accessible to All

Discovery of a Redox Thiol Switch: Implications for Cellular Energy Metabolism

Proteome and phosphoproteome analysis of brown adipocytes reveals that RICTOR loss dampens global insulin/AKT signaling

Large-scale Identification of N-linked Intact Glycopeptides in Human Serum using HILIC Enrichment and Spectral Library Search

Selection of features with consistent profiles improves relative protein quantification in mass spectrometry experiments

Profiling Cell Signaling Networks at Single-cell Resolution

Quantitative Profiling of the Human Substantia Nigra Proteome from Laser-capture Microdissected FFPE Tissue

DEqMS: a method for accurate variance estimation in differential protein expression analysis

Virtual Issue: Technological Innovations

Compliance Checklists No Longer Required at Initial Manuscript Submission

Improving Identification of In-organello Protein-Protein Interactions Using an Affinity-enrichable, Isotopically Coded, and Mass Spectrometry-cleavable Chemical Crosslinker

MaxQuant software for ion mobility enhanced shotgun proteomics

An Improved Boosting to Amplify Signal with Isobaric Labeling (iBASIL) Strategy for Precise Quantitative Single-cell Proteomics

Acquiring and Analyzing Data Independent Acquisition Proteomics Experiments without Spectrum Libraries

A Compact Quadrupole-Orbitrap Mass Spectrometer with FAIMS Interface Improves Proteome Coverage in Short LC Gradients

Proximity Dependent Biotinylation: Key Enzymes and Adaptation to Proteomics Approaches

Microsoft delivers fixes for 110 bugs in April, 2020 Patch Tuesday

Rising to the challenge in the worst circumstances

XG Firewall is now available on AWS

The finish line: Attachment of Signs

The Finish Line: Katrina One Year After

The Finish Line: Cast Stone and EIFS

The Finish Line: Changing Stucco to EIFS

The Finish Line: All About Rust

The Finish Line: Floor Line Joints

The Finish Line: FAQ's About EIFS Part 1

The Finish Line: Types of EIFS

The Finish Line: Eco-Friendliness of EIFS

The Finish Line: Foam Shapes Revisited

The Finish Line: Firestopping

The Finish Line: EPS Vs. Polyisocyanurate Insulation

The Finish Line: A (Faux) Monument for the Ages

The Finish Line: EIFS Inspection

The Finish Line: Building Walls in the Land Down Under

Subscribe To Our Newsletter