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Tropomyosin

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https://www.readbyqxmd.com/read/28913715/oxidized-low-density-lipoprotein-oxldl-affects-load-free-cell-shortening-of-cardiomyocytes-in-a-proprotein-convertase-subtilisin-kexin-9-pcsk9-dependent-way
#1
Klaus-Dieter Schlüter, Annemarie Wolf, Martin Weber, Rolf Schreckenberg, Rainer Schulz
Recent studies have documented that oxidized low-density lipoprotein cholesterol (oxLDL) levels directly impact myocardial structure and function. However, the molecular mechanisms by which oxLDL affects cardiac myocytes are not well established. We addressed the question whether oxLDL modifies load-free cell shortening, a standardized readout of cardiac cellular function, and investigated whether proprotein convertase subtilisin/kexin-9 (PCSK9) is involved on oxLDL-dependent processes. Adult rat ventricular cardiomyocytes were isolated and incubated for 24 h with oxLDL...
September 14, 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28903042/distortion-of-the-actin-a-triad-results-in-contractile-disinhibition-and-cardiomyopathy
#2
Meera C Viswanathan, William Schmidt, Michael J Rynkiewicz, Karuna Agarwal, Jian Gao, Joseph Katz, William Lehman, Anthony Cammarato
Striated muscle contraction is regulated by the movement of tropomyosin over the thin filament surface, which blocks or exposes myosin binding sites on actin. Findings suggest that electrostatic contacts, particularly those between K326, K328, and R147 on actin and tropomyosin, establish an energetically favorable F-actin-tropomyosin configuration, with tropomyosin positioned in a location that impedes actomyosin associations and promotes relaxation. Here, we provide data that directly support a vital role for these actin residues, termed the A-triad, in tropomyosin positioning in intact functioning muscle...
September 12, 2017: Cell Reports
https://www.readbyqxmd.com/read/28894299/dhea-inhibits-acute-microglia-mediated-inflammation-through-activation-of-the-trka-akt1-2-creb-jmjd3-pathway
#3
V I Alexaki, G Fodelianaki, A Neuwirth, C Mund, A Kourgiantaki, E Ieronimaki, K Lyroni, M Troullinaki, C Fujii, W Kanczkowski, A Ziogas, M Peitzsch, S Grossklaus, B Sönnichsen, A Gravanis, S R Bornstein, I Charalampopoulos, C Tsatsanis, T Chavakis
Dehydroepiandrosterone (DHEA) is the most abundant circulating steroid hormone in humans, produced by the adrenals, the gonads and the brain. DHEA was previously shown to bind to the nerve growth factor receptor, tropomyosin-related kinase A (TrkA), and to thereby exert neuroprotective effects. Here we show that DHEA reduces microglia-mediated inflammation in an acute lipopolysaccharide-induced neuro-inflammation model in mice and in cultured microglia in vitro. DHEA regulates microglial inflammatory responses through phosphorylation of TrkA and subsequent activation of a pathway involving Akt1/Akt2 and cAMP response element-binding protein...
September 12, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28887487/trkb-enhancer-facilitates-functional-recovery-after-traumatic-brain-injury
#4
John Marshall, Joanna Szmydynger-Chodobska, Mengia S Rioult-Pedotti, Kara Lau, Andrea T Chin, Siva K Reddy Kotla, Rakesh Kumar Tiwari, Keykavous Parang, Steven W Threlkeld, Adam Chodobski
Brain-derived neurotrophic factor (BDNF), a key player in regulating synaptic strength and learning, is dysregulated following traumatic brain injury (TBI), suggesting that stimulation of BDNF signaling pathways may facilitate functional recovery. This study investigates whether CN2097, a peptidomimetic ligand which targets the synaptic scaffold protein, postsynaptic density protein 95, to enhance downstream signaling of tropomyosin-related kinase B, a receptor for BDNF, can improve neurological function after TBI...
September 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28882412/a-flavonoid-agonist-of-the-trkb-receptor-for-bdnf-improves-hippocampal-neurogenesis-and-hippocampus-dependent-memory-in-the-ts65dn-mouse-model-of-ds
#5
Fiorenza Stagni, Andrea Giacomini, Sandra Guidi, Marco Emili, Beatrice Uguagliati, Maria Elisa Salvalai, Valeria Bortolotto, Mariagrazia Grilli, Roberto Rimondini, Renata Bartesaghi
Intellectual disability is the unavoidable hallmark of Down syndrome (DS), with a heavy impact on public health. Reduced neurogenesis and impaired neuron maturation are considered major determinants of altered brain function in DS. Since the DS brain starts at a disadvantage, attempts to rescue neurogenesis and neuron maturation should take place as soon as possible. The brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays a key role in brain development by specifically binding to tropomyosin-related kinase receptor B (TrkB)...
September 4, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28872999/analysis-of-the-early-cellular-and-humoral-responses-of-galleria-mellonella-larvae-to-infection-by-candida-albicans
#6
Gerard Sheehan, Kevin Kavanagh
Galleria mellonella larvae were administered an inoculum of Candida albicans and the response to infection over 24 hours was monitored. The yeast cell density in infected larvae declined initially but replication commenced six hours post-infection. The hemocyte density decreased from 5.2 × 106/ml to 2.5 × 106/ml at 2 hours but increased to 4.2 × 106 at 6 hours and decreased subsequently. Administration of β - glucan to larvae also caused a fluctuation in hemocyte density (5.1 ± 0.22 × 106/ml (0 hour) to 6...
September 5, 2017: Virulence
https://www.readbyqxmd.com/read/28870922/hedgehog-inhibition-upregulates-trk-expression-to-antagonize-tumor-suppression-in-small-cell-lung-cancer-cells
#7
Hideya Onishi, Katsuya Nakamura, Shuntaro Nagai, Kosuke Yanai, Akio Yamasaki, Makoto Kawamoto, Akira Imaizumi, Takashi Morisaki
BACKGROUND/AIM: Previously we have shown that tropomyosin-related kinase B (TRKB) and Hedgehog (Hh) signalling pathways induce malignant phenotypes in many cancer types. However, results from small cell lung cancer (SCLC) clinical trials using TRK and Hh inhibitors have been disappointing. One reason for this may be the existence of crosstalk between TRKB and Hh signalling pathways. In this study, we detected negative crosstalk between the TRKB and Hh-GLI1 signalling pathways. MATERIALS AND METHODS: The human small cell lung carcinoma cell line, SBC-5, was used...
September 2017: Anticancer Research
https://www.readbyqxmd.com/read/28867488/quaking-rna-binding-proteins-control-early-myofibril-formation-by-modulating-tropomyosin
#8
Aline Bonnet, Guillaume Lambert, Sylvain Ernest, François Xavier Dutrieux, Fanny Coulpier, Sophie Lemoine, Riadh Lobbardi, Frédéric Marc Rosa
Skeletal muscle contraction is mediated by myofibrils, complex multi-molecular scaffolds structured into repeated units, the sarcomeres. Myofibril structure and function have been extensively studied, but the molecular processes regulating its formation within the differentiating muscle cell remain largely unknown. Here we show in zebrafish that genetic interference with the Quaking RNA-binding proteins disrupts the initial steps of myofibril assembly without affecting early muscle differentiation. Using RNA sequencing, we demonstrate that Quaking is required for accumulation of the muscle-specific tropomyosin-3 transcript, tpm3...
September 11, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28865029/juxtanuclear-drebrin-enriched-zone
#9
Wiebke K Ludwig-Peitsch
Drebrin E contributes to remodeling of the actin cytoskeleton and formation of cell processes. Therefore, its role in cell migration was studied in prototypes of motile cells with prominent lamellipodia such as murine B16F1 melanoma and Swiss 3T3 cells and in human SV80 fibroblasts. Confocal microscopy revealed absence of drebrin from the tips of lamellipodia but enrichment in the tail of the cells, in retraction zones and in a specific juxtanuclear actin filament compartment, named "drebrin-enriched zone." A similar subset of juxtanuclear actin filaments is characterized by the actin-binding protein SWAP-70, but drebrin and SWAP-70 localized to different compartments, suggesting the existence of novel distinct subdomains within the actin filament system...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28865016/cell-shape-change-by-drebrin
#10
Kensuke Hayashi
Drebrin is localized in actin-rich regions of neuronal and non-neuronal cells. In mature neurons, its localization is strictly restricted to the postsynaptic sites. In order to understand the function of drebrin in cells, many studies have been performed to examine the effect of overexpression or knocking down of drebrin in various cell types, including neurons, myoblasts, kidney cells, and intestinal epithelial cells. In most cases alteration of cell shape and impairment or facilitation of actin-based activities of these cells were observed...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28865013/biochemistry-of-drebrin-and-its-binding-to-actin-filaments
#11
Ryoki Ishikawa
Drebrin is an actin-binding protein mainly expressed in developing neurons and dendritic spine in mature neurons. To understand the functions of drebrin in vivo, we must understand its molecular properties. In this chapter, I will focus on the purification and characterization of drebrin in vitro. Drebrin binds to F-actin with a stoichiometry of 1:5~6 with a K d of 1~3 × 10(-7) M and strongly inhibits the binding of other actin-binding proteins such as tropomyosin, caldesmon, fascin, α-actinin, and cofilin...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28855298/spinal-bdnf-induced-phrenic-motor-facilitation-requires-pkc%C3%AE-activity
#12
Ibis M Agosto-Marlin, Gordon S Mitchell
Spinal brain derived neurotrophic factor (BDNF) is necessary and sufficient to elicit certain forms of long-lasting phrenic motor facilitation (pMF). BDNF elicits pMF by binding to its high affinity receptor tropomyosin receptor kinase B (TrkB), potentially activating multiple downstream signaling cascades. Canonical BDNF/TrkB signaling includes three pathways: 1) the Ras/RAF/MEK/ERK MAP Kinase pathway; 2) the phosphatidylinositol 3-kinase/Akt pathway; and 3) the PLCγ/PKC pathway. Here, we demonstrate that spinal BDNF-induced pMF requires PLCγ/PKCθ in normal rats, but not MEK/ERK or PI3K/Akt signaling...
August 30, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28834725/crystal-structure-of-leiomodin-2-in-complex-with-actin-a-structural-and-functional-reexamination
#13
Malgorzata Boczkowska, Zeynep Yurtsever, Grzegorz Rebowski, Michael J Eck, Roberto Dominguez
Leiomodins (Lmods) are a family of actin filament nucleators related to tropomodulins (Tmods), which are pointed end-capping proteins. Whereas Tmods have alternating tropomyosin- and actin-binding sites (TMBS1, ABS1, TMBS2, ABS2), Lmods lack TMBS2 and half of ABS1, and present a C-terminal extension containing a proline-rich domain and an actin-binding Wiskott-Aldrich syndrome protein homology 2 (WH2) domain that is absent in Tmods. Most of the nucleation activity of Lmods resides within a fragment encompassing ABS2 and the C-terminal extension...
August 22, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28834398/er-golgi-trafficking-is-facilitated-by-unbranched-actin-filaments-containing-tpm4-2
#14
Anthony J Kee, Nicole S Bryce, Lingyan Yang, Elena Polishchuk, Galina Schevzov, Roberto Weigert, Roman Polishchuk, Peter W Gunning, Edna C Hardeman
We have identified novel actin filaments defined by tropomyosin Tpm4.2 at the ER. EM analysis of mouse embryo fibroblasts (MEFs) isolated from mice expressing a mutant Tpm4.2 (Tpm4(Plt53/Plt53) ), incapable of incorporating into actin filaments, revealed swollen ER structures compared to wild-type (WT) MEFs (Tpm4(+/+) ). ER-to-Golgi, but not Golgi-to-ER trafficking was altered in the Tpm4(Plt53/Plt53) MEFs following the transfection of the temperature sensitive ER-associated ts045-VSVg construct. Exogenous Tpm4...
August 22, 2017: Cytoskeleton
https://www.readbyqxmd.com/read/28831019/multiplex-quantitative-assays-indicate-a-need-for-reevaluating-reported-small-molecule-trkb-agonists
#15
Umed Boltaev, Yves Meyer, Farangis Tolibzoda, Teresa Jacques, Madalee Gassaway, Qihong Xu, Florence Wagner, Yan-Ling Zhang, Michelle Palmer, Edward Holson, Dalibor Sames
Brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin-related kinase B (TrkB), have emerged as key regulators of brain plasticity and represent disease-modifying targets for several brain disorders, including Alzheimer's disease and major depressive disorder. Because of poor pharmacokinetic properties of BDNF, the interest in small-molecule TrkB agonists and modulators is high. Several compounds have been reported to act as TrkB agonists, and their increasing use in various nervous system disorder models creates the perception that these are reliable probes...
August 22, 2017: Science Signaling
https://www.readbyqxmd.com/read/28821448/cognitive-impairment-and-gene-expression-alterations-in-a-rodent-model-of-binge-eating-disorder
#16
Anjali Chawla, Zachary A Cordner, Gretha Boersma, Timothy H Moran
Binge eating disorder (BED) is defined as recurrent, distressing over-consumption of palatable food (PF) in a short time period. Clinical studies suggest that individuals with BED may have impairments in cognitive processes, executive functioning, impulse control, and decision-making, which may play a role in sustaining binge eating behavior. These clinical reports, however, are limited and often conflicting. In this study, we used a limited access rat model of binge-like behavior in order to further explore the effects of binge eating on cognition...
October 15, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28814877/mechanism-and-therapeutic-effectiveness-of-nerve-growth-factor-in-osteoarthritis-pain
#17
REVIEW
Xiushuai Shang, Zhaofei Wang, Hairong Tao
Osteoarthritis (OA) is the most common form of articular joint arthritis and a cause of significant morbidity. In this review, we present the role of nerve growth factor (NGF) in pain generation, relationship between NGF and OA pain, and pathogenic factors (interleukin-1β, transforming growth factor-β1, mechanical loading, and adipokines) involved in OA development. Since NGF blocking is an efficient way to inhibit OA-associated pain, we summarize four categories of drugs that target NGF/tropomyosin receptor kinase A (TrkA) signaling...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/28807678/metformin-lowers-%C3%AE-synuclein-phosphorylation-and-upregulates-neurotrophic-factor-in-the-mptp-mouse-model-of-parkinson-s-disease
#18
Nikita Katila, Sunil Bhurtel, Sina Shadfar, Sunil Srivastav, Sabita Neupane, Uttam Ojha, Gil-Saeng Jeong, Dong-Young Choi
In spite of the massive research for the identification of neurorestorative or neuroprotective intervention for curing Parkinson's disease (PD), there is still lack of clinically proven neuroprotective agents. Metformin, a common anti-hyperglycemic drug has been known to possess neuroprotective properties. However, specific mechanisms by which metformin protects neurons from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity remain to be elucidated. In this study, we assessed the neuroprotective effects of metformin in the subchronic MPTP model of PD, and explored its feasible mechanisms for neuroprotection...
August 12, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28803853/developmental-suppression-of-forebrain-trka-receptors-and-attentional-capacities-in-aging-rats-a-longitudinal-study
#19
Brittney Yegla, Vinay Parikh
Basal forebrain (BF) cholinergic neurons innervating the cortex regulate cognitive, specifically attentional, processes. Cholinergic atrophy and cognitive decline occur at an accelerated pace in age-related neurodegenerative disorders such as Alzheimer's disease; however, the mechanism responsible for this phenomenon remains unknown. Here we hypothesized that developmental suppression of nerve growth factor signaling, mediated via tropomyosin-related kinase A (trkA) receptors, would escalate age-related attentional vulnerability...
September 29, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28793172/tropomyosin-receptor-kinase-a-expression-on-merkel-cell-carcinoma-cells
#20
Ulrike Wehkamp, Sophie Stern, Sandra Krüger, Axel Hauschild, Christoph Röcken, Friederike Egberts
Importance: Merkel cell carcinoma (MCC) is a malignant neuroendocrine skin tumor frequently associated with the Merkel cell polyomavirus. Immune checkpoint therapy showed remarkable results, although not all patients are responsive to this therapy. Anti-tropomyosin receptor kinase A (TrkA)-targeted treatment has shown promising results in several tumor entities. Objective: To determine TrkA expression in MCC as a rationale for potential targeted therapy. Design, Setting, and Participants: This case series study investigated the MCC specimens of 55 patients treated at the Department of Dermatology, University Hospital of Schleswig-Holstein, Kiel, Germany, from January 1, 2005, through December 31, 2015...
August 9, 2017: JAMA Dermatology
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