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https://www.readbyqxmd.com/read/28500241/a-plague-of-actin-disassembly
#1
Shoichiro Ono
Pathogenic Yersinia species employ several strategies to evade the host immune system, including interfering with cytoskeletal remodeling as a way to block macrophage phagocytosis. The kinase YopO binds directly to monomeric actin and phosphorylates the actin-remodeling protein gelsolin, but the functional importance of this gelsolin modification has not been clear. A combined biochemical, computational, and biophysical study now reveals that YopO-mediated phosphorylation activates host gelsolin, leading to severed actin filaments and disturbed actin dynamics...
May 12, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28498470/novel-role-of-semaphorin%C3%A2-3a-in-the-growth-and-progression-of-hepatocellular-carcinoma
#2
Xuedong Li, Qing Chen, Dan Yin, Shiming Shi, Lei Yu, Shaolai Zhou, Erbao Chen, Zhengjun Zhou, Yinghong Shi, Jia Fan, Jian Zhou, Zhi Dai
Semaphorin 3A (SEMA3A), a secretory protein, is a founding member of the semaphorin family and functions in both the biological behavior of tumor cells and the modulation of tumor-associated macrophages. However, the role of SEMA3A in hepatocellular carcinoma (HCC) is still not well established. In the present study, we investigated the expression levels of SEMA3A in 80 HCC tissues and cell lines, using RT-qPCR, western blotting and immunohistochemistry. Expression profile analysis revealed that SEMA3A was significantly overexpressed in human HCC patients and positively correlated with the metastatic potential of HCC cells...
May 2, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28498392/the-flightless-i-protein-interacts-with-rna-binding-proteins-and-is-involved-in-the-genome-wide-mrna-post-transcriptional-regulation-in-lung-carcinoma-cells
#3
Cuihua Wang, Kezhi Chen, Shengyou Liao, Wei Gu, Xinlei Lian, Jing Zhang, Xuejuan Gao, Xiaohui Liu, Tong Wang, Qing-Yu He, Gong Zhang, Langxia Liu
The flightless I protein (FLII) belongs to the gelsolin family. Its function has been associated with actin remodeling, embryonic development, wound repair, and more recently with cancer. The structure of FLII is characterized by the N-terminal leucine-rich repeats (LRR) and C-terminal gesolin related repeated units that are both protein-protein inter-action domains, suggesting that FLII may exert its function by interaction with other proteins. Therefore, systematic study of protein interactions of FLII in cells is important for the understanding of FLII functions...
May 11, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28469748/plasma-actin-gelsolin-and-orosomucoid-levels-after-eccentric-exercise
#4
Éva Tékus, Márk Váczi, Zoltán Horváth-Szalai, Andrea Ludány, Tamás Kőszegi, Márta Wilhelm
The present study investigated the acute effect of eccentric exercise on blood plasma actin, gelsolin (GSN) and orosomucoid (AGP) levels in untrained and moderately trained individuals, and their correlation with exercise induced muscle damage (EIMD) markers (CK, intensity of muscle soreness and maximal voluntary contraction torque deficit). Healthy physical education students (6 untrained, 12 moderately trained) participated in this research. Actin, GSN, AGP and CK levels were measured in blood plasma at baseline, immediately, 1 h, 6 h and 24 h post-exercise comprising 90 eccentric quadriceps contractions performed on a dynamometer...
February 2017: Journal of Human Kinetics
https://www.readbyqxmd.com/read/28465181/expression-purification-and-characterization-of-recombinant-8%C3%A2-kda-gelsolin-fragment
#5
Qing Zhang, Weijie Lu, Lina Ji, Zi-Chun Hua
A mutation (D187N/Y) in human plasma gelsolin (GSN) leads to the generation of an 8 kDa GSN fragment (8 kDa-GSN), and consequently causes the familial amyloidosis of Finnish type. Because of its faster kinetics of amyloid formation under physiologically relevant conditions, 8 kDa-GSN is used to explore gelsolin amyloidosis and screen small molecules that can disaggregate amyloids. However, the synthetic 8 kDa-GSN is expensive, and substantial quantities of 8 kDa-GSN are needed for the screen. Here we report a study to obtain recombinant 8 kDa-GSN with high yield from Escherichia coli...
April 29, 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28455686/flightless-i-homolog-regulates-glucocorticoid-receptor-mediated-transcription-via-direct-interaction-of-the-leucine-rich-repeat-domain
#6
Hong Lan Jin, Liu Yang, Kwang Won Jeong
Flightless-I homolog (FLII) is a member of the gelsolin family of proteins, and has been identified as a coactivator of estrogen receptor-mediated transcription. Here, we investigate the role of FLII in the glucocorticoid receptor (GR) signaling pathway. Reporter gene assay and real-time quantitative PCR in A549 were performed to investigate the function of FLII in the expression of GR target genes. Co-immunoprecipitation assay and in vitro binding assay were used to identify binding domain of FLII. Chromatin immunoprecipitation assay were carried out with FLII-depleted A549 cells to determine the role of FLII at GR binding sites...
April 28, 2017: Molecular Biology Reports
https://www.readbyqxmd.com/read/28440466/mir-200a-targets-gelsolin-a-novel-mechanism-regulating-secretion-of-microvesicles-in-hepatocellular-carcinoma-cells
#7
Ya Xu, Yanfen Zhang, Lujing Wang, Ruiqi Zhao, Yu Qiao, Dong Han, Qian Sun, Nazhen Dong, Yicong Liu, Dantong Wu, Xuemei Zhang, Ning Huang, Ning Ma, Weiming Zhao, Yanhong Liu, Xu Gao
Microvesicle biogenesis is a highly regulated process. Aberrant release of microvesicles from cancer cells have been associated with their invasiveness and prognosis. However, the mechanism of aberrant release remains poorly understood. Herein, we found that hepatocellular carcinoma cells shed more microvesicles than normal hepatocytes and miR-200a were shown to inhibit the release of microvesicles in hepatocellular carcinoma cells. Then, we confirmed that miR-200a might target Gelsolin and change cytoskeleton to regulate microvesicles secretion...
May 2017: Oncology Reports
https://www.readbyqxmd.com/read/28431142/respiratory-chain-enzyme-deficiency-induces-mitochondrial-location-of-actin-binding-gelsolin-to-modulate-the-oligomerization-of-vdac-complexes-and-cell-survival
#8
Alberto García-Bartolomé, Ana Peñas, Lorena Marín-Buera, Teresa Lobo-Jarne, Rafael Pérez-Pérez, María Morán, Joaquín Arenas, Miguel A Martín, Cristina Ugalde
Despite considerable knowledge on the genetic basis of mitochondrial disorders, their pathophysiological consequences remain poorly understood. We previously used 2D-DIGE analyses to define a protein profile characteristic for respiratory chain complex III-deficiency that included a significant overexpression of cytosolic Gelsolin (GSN), a cytoskeletal protein that regulates the severing and capping of the actin filaments. Biochemical and immunofluorescence assays confirmed a specific increase of GSN levels in the mitochondria from patientś fibroblasts and from transmitochondrial cybrids with complex III assembly defects...
April 18, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28404947/identification-of-urine-biomarkers-associated-with-lung-adenocarcinoma
#9
Weiwei Wang, Shanshan Wang, Man Zhang
Lung adenocarcinoma (LAC) progression is accompanied by changes in protein levels that may be reflected in body fluids, such as urine. Urine collected from LAC patients (n=34) and healthy controls (n=36) was analyzed via matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) combined with weak cationic exchange magnetic beads. The results revealed 76 urinary polypeptides significantly different between LAC patients and normal controls (P<0.05). Twenty-two of these peptides were up-regulated and 54 were down-regulated...
March 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28400331/four-paralog-gelsolin-genes-are-differentially-expressed-in-the-earthworm-lumbricus-terrestris
#10
Prasath Thiruketheeswaran, Paul Thomalla, Evelyn Krüger, Horst Hinssen, Jochen D'Haese
We have identified and characterized four distinct variants of the gelsolin-related protein (EWAM P1-P4) in the earthworm L. terrestris. All of these proteins biochemically qualify as gelsolins since they sever actin filaments in a calcium dependent manner. P1, P2 and P3 are present in the Lumbricus body wall muscle whereas in the gizzard muscle P3 and P4 were found. P1-P4 are encoded by four paralog genes and are differentially expressed in various muscle cell tissues. While the genes for P1 and P2 contain one intron, there was no intron in both P3 and P4 genes...
April 8, 2017: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/28385809/free-actin-impairs-macrophage-bacterial-defenses-via-scavenger-receptor-marco-interaction-with-reversal-by-plasma-gelsolin
#11
Christine M Ordija, Terry Ting-Yu Chiou, Zhiping Yang, Glen M Deloid, Melina de Oliveira Valdo, Zhi Wang, Alice Bedugnis, Terry L Noah, Samuel Jones, Henry Koziel, Lester Kobzik
Lung injury can release intracellular actin into the alveolar milieu, and is also associated with increased susceptibility to secondary infections. We investigated the effect of free (extracellular) actin on lung macrophage host defense functions. Western blot analysis demonstrated free actin release into the lung lavage fluids of mouse models of ozone injury, influenza infection and secondary pneumococcal pneumonia, and in samples from patients following burn and inhalation injury. Using levels comparable to those observed in lung injury, we found that free actin markedly inhibited murine lung macrophage binding and uptake in vitro of S...
April 6, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28377587/overexpression-of-gsn-could-decrease-inflammation-and-apoptosis-in-eae-and-may-enhance-vitamin-d-therapy-on-eae-ms
#12
Jifang Gao, Zhaoyu Qin, Xinyuan Guan, Juanjuan Guo, Huaqing Wang, Shilian Liu
The decrease of gelsolin (GSN) in the blood has been reported in multiple sclerosis (MS) patients and experimental allergic encephalomyelitis (EAE) animals, but the protective effect of GSN on EAE/MS lacks of evidence. In our study, we increased the GSN level in EAE by injecting GSN-overexpress lentivirus (LV-GSN) into the lateral ventricle and caudal vein and found that GSN administration can delay the onset and decrease the severity of EAE. Vitamin D is proven to have a therapeutic effect on MS/EAE; however, we previously found that vitamin D caused a downregulation of GSN, which might limit vitamin D efficacy...
April 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28365030/serum-gelsolin-levels-in-aneurismal-subarachnoid-hemorrhage-preliminary-results
#13
A Rodríguez-Rodríguez, J J Egea-Guerrero, Z Ruiz de Azúa-López, G Rivera-Rubiales, Á Vilches-Arenas, F Murillo-Cabezas
No abstract text is available yet for this article.
March 29, 2017: Medicina Intensiva
https://www.readbyqxmd.com/read/28357579/epithelial-cell-types-and-their-proposed-roles-in-maintaining-the-mucosal-barrier-in-human-chagasic-megacolonic-mucosa
#14
Christian Koch, Alexandre B M da Silveira, Enio C de Oliveira, Karl Quint, Winfried Neuhuber, Axel Brehmer, Samir Jabari
Patients suffering from chagasic megacolon must have an intact mucosal barrier as they survive this chronic disease for decades. A key structure of the mucosal barrier are epithelial cells. Vasoactive-intestinal-peptide (VIP)-positive nerve fibres are involved in influencing, e.g., epithelial cell proliferation, mucus secretion (e.g., mucin 2 and trefoil factor 3 of goblet cells) and inflammation or autoimmunity, all putative and/or known factors altered in chagasic megacolon. We analyzed qualitatively and quantitatively goblet cells, their specific markers, such as mucin 2 (MUC2) and trefoil factor 3 (TFF3) and enterocytes, the relation of VIP-immunoreactive nerve fibres to the epithelia, the distribution of gelsolin, a protein involved in chronic inflammation processes in the epithelia, and the proliferation rate of epithelial cells by combined 4',6-diamidino-2-phenylindole (DAPI) and phosphohistone-H3 (PHH3) staining...
March 29, 2017: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/28349924/structural-basis-for-ph-mediated-regulation-of-f-actin-severing-by-gelsolin-domain-1
#15
Jing-Song Fan, Honzhen Goh, Ke Ding, Bo Xue, Robert C Robinson, Daiwen Yang
Six-domain gelsolin regulates actin structural dynamics through its abilities to sever, cap and uncap F-actin. These activities are modulated by various cellular parameters like Ca(2+) and pH. Until now, only the molecular activation mechanism of gelsolin by Ca(2+) has been understood relatively well. The fragment comprising the first domain and six residues from the linker region into the second domain has been shown to be similar to the full-length protein in F-actin severing activity in the absence of Ca(2+) at pH 5...
March 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28344658/flightless-i-governs-cell-fate-by-recruiting-the-sumo-isopeptidase-senp3-to-distinct-hox-genes
#16
Arnab Nayak, Anja Reck, Christian Morsczeck, Stefan Müller
BACKGROUND: Despite recent studies on the role of ubiquitin-related SUMO modifier in cell fate decisions, our understanding on precise molecular mechanisms of these processes is limited. Previously, we established that the SUMO isopeptidase SENP3 regulates chromatin assembly of the MLL1/2 histone methyltransferase complex at distinct HOX genes, including the osteogenic master regulator DLX3. A comprehensive mechanism that regulates SENP3 transcriptional function was not understood. RESULTS: Here, we identified flightless-I homolog (FLII), a member of the gelsolin family of actin-remodeling proteins, as a novel regulator of SENP3...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28343311/mechanistic-insight-of-platelet-apoptosis-leading-to-non-surgical-bleeding-among-heart-failure-patients-supported-by-continuous-flow-left-ventricular-assist-devices
#17
Nandan K Mondal, Tielou Li, Zengsheng Chen, Hegang H Chen, Erik N Sorensen, Si M Pham, Michael A Sobieski, Steven C Koenig, Mark S Slaughter, Bartley P Griffith, Zhongjun J Wu
Non-surgical bleeding (NSB) is the most common clinical complication in heart failure (HF) patients supported by continuous-flow left ventricular assist devices (CF-LVADs). In this study, oxidative stress and alteration of signal pathways leading to platelet apoptosis were investigated. Thirty-one HF patients supported by CF-LVADs were divided into bleeder (n = 12) and non-bleeder (n = 19) groups. Multiple blood samples were collected at pre-implant (baseline) and weekly up to 1-month post-implant. A single blood sample was collected from healthy subjects (reference)...
March 25, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28334940/aav9-delivered-bispecific-nanobody-attenuates-amyloid-burden-in-the-gelsolin-amyloidosis-mouse-model
#18
Adriaan Verhelle, Nisha Nair, Inge Everaert, Wouter Van Overbeke, Lynn Supply, Olivier Zwaenepoel, Cindy Peleman, Jo Van Dorpe, Tony Lahoutte, Nick Devoogdt, Wim Derave, Marinee K Chuah, Thierry Vanden Driessche, Jan Gettemans
Gelsolin amyloidosis is a dominantly inherited, incurable type of amyloidosis. A single point mutation in the gelsolin gene (G654A is most common) results in the loss of a Ca2+  binding site in the second gelsolin domain. Consequently, this domain partly unfolds and exposes an otherwise buried furin cleavage site at the surface. During secretion of mutant plasma gelsolin consecutive cleavage by furin and MT1-MMP results in the production of 8 and 5 kDa amyloidogenic peptides. Nanobodies that are able to (partly) inhibit furin or MT1-MMP proteolysis have previously been reported...
April 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28331304/does-urinary-peptide-content-differ-between-copd-patients-with-and-without-inherited-alpha-1-antitrypsin-deficiency
#19
Alfonso Carleo, Joanna Chorostowska-Wynimko, Thomas Koeck, Harald Mischak, Małgorzata Czajkowska-Malinowska, Adriana Rozy, Tobias Welte, Sabina Janciauskiene
Differentiating between chronic obstructive pulmonary disease (COPD) patients with normal (PiMM) or deficient (PiZZ) genetic variants of alpha-1 antitrypsin (A1AT) is important not only for understanding the pathobiology of disease progression but also for improving personalized therapies. This pilot study aimed to investigate whether urinary peptides reflect the A1AT-related phenotypes of COPD. Urine samples from 19 clinically stable COPD cases (7 PiMM and 12 PiZZ A1AT) were analyzed by capillary electrophoresis coupled to mass spectrometry...
2017: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/28255017/cdk6-contributes-to-cytoskeletal-stability-in-erythroid-cells
#20
Iris Z Uras, Ruth M Scheicher, Karoline Kollmann, Martin Glösmann, Michaela Prchal-Murphy, Anca S Tigan, Daniela A Fux, Sandro Altamura, Joana Neves, Martina Muckenthaler, Keiryn L Bennett, Stefan Kubicek, Philip W Hinds, Marieke von Lindern, Veronika Sexl
Mice lacking Cdk6 kinase activity suffer from mild anemia accompanied by elevated numbers of Ter119+ cells in the bone marrow. The animals show hardly any alterations in erythroid development, indicating that Cdk6 is not required for proliferation and maturation of erythroid cells. There is also no difference in stress erythropoiesis following hemolysis in vivo. However, Cdk6-/- erythrocytes have a shortened lifespan and are more sensitive to mechanical stress in vitro, suggesting differences in the cytoskeletal architecture...
March 2, 2017: Haematologica
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