Search results for "oligo"
showing 10 items of 1298 documents
Long Term Culture of the A549 Cancer Cell Line Promotes Multilamellar Body Formation and Differentiation towards an Alveolar Type II Pneumocyte Pheno…
2016
Pulmonary research requires models that represent the physiology of alveolar epithelium but concerns with reproducibility, consistency and the technical and ethical challenges of using primary or stem cells has resulted in widespread use of continuous cancer or other immortalized cell lines. The A549 'alveolar' cell line has been available for over four decades but there is an inconsistent view as to its suitability as an appropriate model for primary alveolar type II (ATII) cells. Since most work with A549 cells involves short term culture of proliferating cells, we postulated that culture conditions that reduced proliferation of the cancer cells would promote a more differentiated ATII ce…
MOBP levels are regulated by Fyn kinase and affect the morphological differentiation of oligodendrocytes.
2015
Oligodendrocytes are the myelinating glial cells of the central nervous system (CNS). Myelin is formed by extensive wrapping of oligodendroglial processes around axonal segments which ultimately allows a rapid saltatory conduction of action potentials within the CNS and sustains neuronal health. The non-receptor tyrosine kinase Fyn is an important signaling molecule in oligodendrocytes. It controls the morphological differentiation of oligodendrocytes and is an integrator of axon-glial signaling cascades leading to localized synthesis of Myelin Basic Protein (MBP) which is essential for myelin formation. The abundant Myelin-Associated Oligodendrocytic Basic Protein (MOBP) resembles MBP in s…
Neurofibromatosis type 2 tumor suppressor protein is expressed in oligodendrocytes and regulates cell proliferation and process formation.
2017
The neurofibromatosis type 2 (NF2) tumor suppressor protein Merlin functions as a negative regulator of cell growth and actin dynamics in different cell types amongst which Schwann cells have been extensively studied. In contrast, the presence and the role of Merlin in oligodendrocytes, the myelin forming cells within the CNS, have not been elucidated. In this work, we demonstrate that Merlin immunoreactivity was broadly distributed in the white matter throughout the central nervous system. Following Merlin expression during development in the cerebellum, Merlin could be detected in the cerebellar white matter tract at early postnatal stages as shown by its co-localization with Olig2-positi…
Myelin: Methods for Purification and Proteome Analysis
2019
Molecular characterization of myelin is a prerequisite for understanding the normal structure of the axon/myelin-unit in the healthy nervous system and abnormalities in myelin-related disorders. However, reliable molecular profiles necessitate very pure myelin membranes, in particular when considering the power of highly sensitive "omics"-data acquisition methods. Here, we recapitulate the history and recent applications of myelin purification. We then provide our laboratory protocols for the biochemical isolation of a highly pure myelin-enriched fraction from mouse brains and for its proteomic analysis. We also supply methodological modifications when investigating posttranslational modifi…
1-ethyl-3-(6-methylphenanthridine-8-il) urea modulates TLR3/9 activation and induces selective pro-inflammatory cytokine expression in vitro.
2017
We have previously demonstrated the nucleic acid binding capacity of phenanthridine derivatives (PHTs). Because nucleic acids are potent inducers of innate immune response through Toll-like receptors (TLRs), and because PTHs bear a structural resemblance to commonly used synthetic ligands for TLR7/8, we hypothesized that PHTs could modulate/activate immune response. We found that compound M199 induces secretion of IL-6, IL-8 and TNFα in human PBMCs and inhibits TLR3/9 activation in different cellular systems (PBMCs, HEK293 and THP-1 cell lines).
Dual role of the RNA helicase DDX5 in post-transcriptional regulation of Myelin Basic Protein in oligodendrocytes
2017
In the central nervous system, oligodendroglial expression of Myelin Basic Protein (MBP) is crucial for the assembly and structure of the myelin sheath. MBP synthesis is tightly regulated in space and time, particularly on the post-transcriptional level. We have identified the DEAD-box RNA helicase DDX5 (alias p68) in a complex with Mbp mRNA in oligodendroglial cells. Expression of DDX5 is highest in progenitor cells and immature oligodendrocytes, where it localizes to heterogeneous populations of cytoplasmic ribonucleoprotein (RNP) complexes associated with Mbp mRNA in the cell body and processes. Manipulation of DDX5 protein amounts inversely affects levels of MBP protein. We present evid…
Membrane chaperoning by members of the PspA/IM30 protein family
2017
ABSTRACTPspA, IM30 (Vipp1) and LiaH, which all belong to the PspA/IM30 protein family, form high molecular weight oligomeric structures. For all proteins membrane binding and protection of the membrane structure and integrity has been shown or postulated. Here we discuss the possible membrane chaperoning activity of PspA, IM30 and LiaH and propose that larger oligomeric structures bind to stressed membrane regions, followed by oligomer disassembly and membrane stabilization by protein monomers or smaller/different oligomeric scaffolds.
Myotonic dystrophy type 1 drug development: A pipeline toward the market
2021
Highlights • Myotonic dystrophy, a neuromuscular disease, affects at least around half a million people worldwide. • Close to two dozen preclinical and clinical drug development programs active. • Drugs encompass new chemical entities, repurposing, oligonucleotide, and gene therapy. • Tideglusib, mexiletine, and metformin are close to reaching marketing authorization.
Retene causes multifunctional transcriptomic changes in the heart of rainbow trout (Oncorhynchus mykiss) embryos
2015
Fish are particularly sensitive to aryl hydrocarbon receptor (AhR)-mediated developmental toxicity. The molecular mechanisms behind these adverse effects have remained largely unresolved in salmonids, and for AhR-agonistic polycyclic aromatic hydrocarbons (PAHs). This study explored the cardiac transcriptome of rainbow trout (Oncorhynchus mykiss) eleuteroembryos exposed to retene, an AhR-agonistic PAH. The embryos were exposed to retene (nominal concentration 32 μg/L) and control, their hearts were collected before, at and after the onset of the visible signs of developmental toxicity, and transcriptomic changes were studied by microarray analysis. Retene up- or down-regulated 122 genes. Th…
Pharmacokinetics and Pharmacodynamics of a 13-mer LNA-inhibitor-miR-221 in Mice and Non-human Primates
2016
Locked nucleic acid (LNA) oligonucleotides have been successfully used to efficiently inhibit endogenous small noncoding RNAs in vitro and in vivo. We previously demonstrated that the direct miR-221 inhibition by the novel 13-mer LNA-i-miR-221 induces significant antimyeloma activity and upregulates canonical miR-221 targets in vitro and in vivo. To evaluate the LNA-i-miR-221 pharmacokinetics and pharmacodynamics, novel assays for oligonucleotides quantification in NOD.SCID mice and Cynomolgus monkeys (Macaca fascicularis) plasma, urine and tissues were developed. To this aim, a liquid chromatography/mass spectrometry method, after solid-phase extraction, was used for the detection of LNA-i…