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https://www.readbyqxmd.com/read/28513458/cofilin-a-protein-controlling-dynamics-of-actin-filaments
#1
Zofia Ostrowska, Joanna Moraczewska
Cofilins are evolutionary conserved proteins present in all Eukaryotic cells. Their primary function is dynamic reorganization of actin cytoskeleton. Two cofilin isoforms are known: cofilin 1, present in all studied non-muscle cells and in embryonic muscle cells, and cofilin 2, which dominates in mature skeletal and cardiac muscles. Polypeptide chains of both isoforms fold into a structure homological to a conservative ADF (actin depolymerizing factor) domain, which is characteristic of actin depolymerizing factor...
May 5, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28502459/discovery-of-indolin-2-one-derivatives-as-potent-pak4-inhibitors-structure-activity-relationship-analysis-biological-evaluation-and-molecular-docking-study
#2
Jing Guo, Mingyue Zhu, Tianxiao Wu, Chenzhou Hao, Kai Wang, Zizheng Yan, Wanxu Huang, Jian Wang, Dongmei Zhao, Maosheng Cheng
Utilizing a pharmacophore hybridization approach, a novel series of substituted indolin-2-one derivatives were designed, synthesized and evaluated for their in vitro biological activities against p21-activated kinase 4. Compounds 11b, 12d and 12g exhibited the most potent inhibitory activity against PAK4 (IC50=22nM, 16nM and 27nM, respectively). Among them, compound 12g showed the highest antiproliferative activity against A549 cells (IC50=0.83μM). Apoptosis analysis in A549 cells suggested that compound 12g delayed cell cycle progression by arresting cells in the G2/M phase of the cell cycle, retarding cell growth...
May 3, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28502289/the-chronophin-activation-is-necessary-in-doxorubicin-induced-actin-cytoskeleton-alteration
#3
Su Jin Lee, Jeen Woo Park, Beom Sik Kang, Dong-Seok Lee, Hyun-Shik Lee, Sooyoung Choi, Oh-Shin Kwon
Although it is known that doxorubicin (Dox)-induced oxidative stress is associated with its cytotoxicity, the precise mechanism remains unclear. Genotoxic stress not only generates free radicals but also affects actin cytoskeleton stability. We showed that Dox-induced RhoA signaling stimulated actin cytoskeleton alterations resulting in central stress fiber disruption at early time points and later cortical actin formation at the cell periphery in HeLa cells. Interestingly, activation of a cofilin phosphatase, chronophin (CIN), was initially evoked by Dox-induced RhoA signaling, resulting in a rapid phosphorylated cofilin turnover leading to actin cytoskeleton remodeling...
May 15, 2017: BMB Reports
https://www.readbyqxmd.com/read/28499611/silver-nanoparticle-induced-phosphorylation-of-histone-h3-at-serine-10-is-due-to-dynamic-changes-in-actin-filaments-and-the-activation-of-aurora-kinases
#4
Xiaoxu Zhao, Tatsushi Toyooka, Yuko Ibuki
The phosphorylation of histone H3 at serine 10 (p-H3S10) has been closely correlated with mitotic chromosome condensation. We previously reported that silver nanoparticles (AgNPs) significantly induced p-H3S10 independent of mitosis. In the present study, we examined the mechanisms underlying the induction of p-H3S10 by AgNPs. A treatment with AgNPs markedly induced p-H3S10 in a dose-dependent manner in three types of cell lines, and this was dependent on the cellular incorporation of AgNPs. The immunofluorescent staining of AgNP-induced p-H3S10 was thin and solid throughout the nucleus, and differed from that normally associated with mitosis...
May 10, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28497946/nanopillar-surface-topology-promotes-cardiomyocyte-differentiation-through-cofilin-mediated-cytoskeleton-rearrangement
#5
Ha-Rim Seo, Hyung Joon Joo, Dae Hwan Kim, Long-Hui Cui, Seung-Cheol Choi, Jong-Ho Kim, Sung Woo Cho, Kyu Back Lee, Do-Sun Lim
Nanoscaled surface patterning is an emerging potential method of directing the fate of stem cells. We adopted nanoscaled pillar gradient patterned cell culture plates with three diameter gradients [280-360 (GP 280/360), 200-280 (GP 200/280), and 120-200 nm (GP 120/200)] and investigated their cell fate-modifying effect on multipotent fetal liver kinase 1-positive mesodermal precursor cells (Flk1(+) MPCs) derived from embryonic stem cells. We observed increased cell proliferation and colony formation of the Flk1(+) MPCs on the nanopattern plates...
May 12, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28489960/swap70-is-a-universal-gef-like-adapter-for-tethering-actin-to-phagosomes
#6
Maksim V Baranov, Natalia H Revelo, Daniëlle R J Verboogen, Martin Ter Beest, Geert van den Bogaart
We recently identified a key role for SWAP70 as the tethering factor stabilizing F-actin filaments on the surface of phagosomes in human dendritic cells by interacting both with Rho-family GTPases and the lipid phosphatidylinositol (3,4)-bisphosphate. In this study, we aimed to investigate whether this role of SWAP70 was general among immune phagocytes. Our data reveal that SWAP70 is recruited to early phagosomes of macrophages and dendritic cells from both human and mouse. The putative inhibitor of SWAP70 sanguinarine blocked phagocytosis and F-actin polymerization, supporting a key role for SWAP70 in phagocytosis as demonstrated previously with knock-down...
May 10, 2017: Small GTPases
https://www.readbyqxmd.com/read/28487281/filamin-a-is-required-for-spindle-migration-and-asymmetric-division-in-mouse-oocytes
#7
HaiYang Wang, Jing Guo, ZiLi Lin, Suk Namgoong, Jeong Su Oh, Nam-Hyung Kim
Dynamic changes in the actin network are crucial for the cortical migration of spindles and establishment of polarity, to ensure asymmetric division during meiotic maturation. In this study, filamin A (FLNA) was found to be an essential actin regulator that controlled spindle migration and asymmetric division during oocyte meiosis. FLNA was localized in the cytoplasm and enriched at the cortex and near the chromosomes. Knockdown of FLNA impaired meiotic asymmetric division and spindle migration with a decrease in the amount of cytoplasmic actin mesh and cortical actin levels...
May 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28479159/proteomic-analysis-of-filaggrin-deficiency-identifies-molecular-signatures-characteristic-of-atopic-eczema
#8
Martina S Elias, Heather A Long, Carla F Newman, Paul A Wilson, Andrew West, Paul J McGill, Keith C Wu, Michael J Donaldson, Nick J Reynolds
BACKGROUND: Atopic eczema (AE) is characterized by skin barrier and immune dysfunction. Null mutations in filaggrin (FLG), a key epidermal barrier protein, strongly predispose to AE; however, the precise role of FLG deficiency in AE pathogenesis remains incompletely understood. OBJECTIVES: We sought to identify global proteomic changes downstream of FLG deficiency in human epidermal living skin-equivalent (LSE) models and validate findings in skin of patients with AE...
April 28, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28446539/transient-mechanical-strain-promotes-the-maturation-of-invadopodia-and-enhances-cancer-cell-invasion-in-vitro
#9
Alexander N Gasparski, Snehal Ozarkar, Karen A Beningo
Cancer cell invasion is influenced by various biomechanical forces found within the microenvironment. We have previously found that invasion is enhanced in fibrosarcoma cells when transient mechanical stimulation is applied within an in vitro mechano-invasion assay. This enhancement of invasion is dependent on cofilin, a known regulator of invadopodia maturation. Invadopodia are actin-rich structures present in invasive cancer cells that are enzymatically active and degrade the surrounding extracellular matrix to facilitate invasion...
April 26, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28445157/lim-kinases-cofilin-and-beyond
#10
Chloé Prunier, Renaud Prudent, Reuben Kapur, Karin Sadoul, Laurence Lafanechère
LIM kinases are common downstream effectors of several signalization pathways and function as a signaling node that controls cytoskeleton dynamics through the phosphorylation of the cofilin family proteins. These last 10 years, several reports indicate that the functions of LIM kinases are more extended than initially described and, specifically, that LIM kinases also control microtubule dynamics, independently of their regulation of actin microfilament. In this review we analyze the data supporting these conclusions and the possible mechanisms that could be involved in the control of microtubules by LIM kinases...
April 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28440461/the-role-of-mir-451-in-the-switching-between-proliferation-and-migration-in-malignant-glioma-cells-ampk-signaling-mtor-modulation-and-rac1-activation-required
#11
Kai Zhao, Leilei Wang, Tao Li, Meng Zhu, Chen Zhang, Lei Chen, Pengfei Zhao, Hua Zhou, Shengping Yu, Xuejun Yang
Glioblastoma multiforme (GBM), WHO grade IV astrocytoma, is the most common primary neoplasm of the central nervous system (CNS) and has the highest malignancy and mortality rates. The invasive nature of GBM complicates surgical resection and restricts chemotherapeutic access, contributing to poor patient prognosis. The migration of tumor cells is closely related to the tumor cell proliferation. The acquisition of migratory capability, in addition to intracellular factors, is proposed to be a crucial mechanism during the progression of invasion...
April 21, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28440035/mir-145-inhibits-human-colorectal-cancer-cell-migration-and-invasion-via-pak4-dependent-pathway
#12
Nengquan Sheng, Gewen Tan, Weiqiang You, Hongqi Chen, Jianfeng Gong, Di Chen, Huizhen Zhang, Zhigang Wang
MicroRNA-145 (miR-145), as a tumor-suppressive miRNA, has been demonstrated down-regulated in colorectal cancer (CRC) cells, and could inhibit CRC cells growth. However, the molecular pathway in which miR-145 modulates CRC malignant transformation has not been fully revealed. Here, we reported an intense correlation between the expressions of PAK4 and miR-145 in human CRC cell lines. Transwell assay verified overexpression of miR-145, as well as knockdown of PAK4, significantly suppressed cell migration and invasion ability...
April 24, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28422872/effect-of-hsp27-and-cofilin-in-the-injury-of-hypoxia-reoxygenation-on-hepatocyte-membrane-f-actin-microfilaments
#13
Yafei Zhang, Jiazhong Wang, Hong Ji, Hongwei Lu, Le Lu, Jinlong Wang, Yiming Li
Hypoxia-reoxygenation (H/R) injury hepatocyte models were established to simulate the ischemia/reperfusion injury of transplanted organ. Through the study of the molecular mechanism of H/R on the F-actin damage of the liver cytomembrane, the mechanism of F-actin damage induced by ischemia and reperfusion was studied from the level of cell and molecule.The hypoxic environment of cells in vitro was simulated by chemical hypoxia agent CoCl2. Liver cells were detected by MTT, H/R group was subdivided into 3 subgroups: H/R 2, 4, and 6 h...
April 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28416631/mutation-of-neuron-specific-chromatin-remodeling-subunit-baf53b-rescue-of-plasticity-and-memory-by-manipulating-actin-remodeling
#14
Annie Vogel Ciernia, Enikö A Kramár, Dina P Matheos, Robbert Havekes, Thekla J Hemstedt, Christophe N Magnan, Keith Sakata, Ashley Tran, Soraya Azzawi, Alberto Lopez, Richard Dang, Weisheng Wang, Brian Trieu, Joyce Tong, Ruth M Barrett, Rebecca J Post, Pierre Baldi, Ted Abel, Gary Lynch, Marcelo A Wood
Recent human exome-sequencing studies have implicated polymorphic Brg1-associated factor (BAF) complexes (mammalian SWI/SNF chromatin remodeling complexes) in several intellectual disabilities and cognitive disorders, including autism. However, it remains unclear how mutations in BAF complexes result in impaired cognitive function. Post-mitotic neurons express a neuron-specific assembly, nBAF, characterized by the neuron-specific subunit BAF53b. Subdomain 2 of BAF53b is essential for the differentiation of neuronal precursor cells into neurons...
May 2017: Learning & Memory
https://www.readbyqxmd.com/read/28409884/altered-protein-expression-pattern-in-colon-tissue-of-mice-upon-supplementation-with-distinct-selenium-compounds
#15
Jette Rahn, Claudia Lennicke, Anna P Kipp, Andreas S Müller, Ludger A Wessjohann, Rudolf Lichtenfels, Barbara Seliger
The essential trace element Selenium (Se) is controversially discussed concerning its role in health and disease. Its various physiological functions are largely mediated by Se incorporation in the catalytic center of selenoproteins. To gain insights into the impact of Se deficiency and of supplementation with different Se compounds (selenite, selenate, selenomethionine) at defined concentrations (recommended, 150 μg/ kg diet; excessive, 750 μg/ kg diet) in murine colon tissues a twenty week feeding experiment was performed followed by analysis of the protein expression pattern of colon tissue specimens by 2D-DIGE and MALDI-TOF MS...
April 14, 2017: Proteomics
https://www.readbyqxmd.com/read/28404907/investigation-of-three-potential-autoantibodies-in-sjogren-s-syndrome-and-associated-malt-lymphoma
#16
Li Cui, Naseim Elzakra, Shuaimei Xu, Gary Guishan Xiao, Yan Yang, Shen Hu
Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease which might progress to mucosal-associated lymphoid tissue lymphoma (pSS/MALT). Diagnosis of pSS requires an invasive tissue biopsy and a delay in diagnosis of pSS has been frequently reported. In this study, four proteins including cofilin-1, alpha-enolase, annexin A2 and Rho GDP-dissociation inhibitor 2 (RGI2) were found to be over-expressed in pSS and pSS/MALT by 2D gel electrophoresis/mass spectrometry, and the finding was verified by the microarray analysis and western blotting results...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28388575/cofilin-1-induces-the-epithelial-mesenchymal-transition-of-gastric-cancer-cells-by-promoting-cytoskeletal-rearrangement
#17
Wang Haibo, Tao Lide, Jin Feng, Gu Hao, Dai Xiaojun, Ni Tengyang, Feng Jun, Ding Yanbing, Xiao Weiming, Qian Yayun, Liu Yanqing
Epithelial-mesenchymal transition (EMT) is an important biological process whereby malignant tumor cells obtain the ability to migrate, invade, resist apoptosis and degrade the extracellular matrix. We found that Cofilin1 (CFL1) expression was elevated in clinical gastric cancer specimens and correlated with biomarkers of EMT in BGC-823 gastric cancer cells. BGC-823 cells exhibited EMT phenotypes and increased metastatic ability when induced by TGF-β1. By contrast, BGC-823 cells transfected with Lv-siRNA-CFL1 did not exhibit EMT phenotypes under the same inducing conditions...
March 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28386357/fasudil-inhibits-proliferation-and-collagen-synthesis-and-induces-apoptosis-of-human-fibroblasts-derived-from-urethral-scar-via-the-rho-rock-signaling-pathway
#18
Ning Xu, Shao-Hao Chen, Gen-Yi Qu, Xiao-Dong Li, Wen Lin, Xue-Yi Xue, Yun-Zhi Lin, Qing-Shui Zheng, Yong Wei
Fasudil has shown antifibrotic effects in various fibrotic diseases. However, its effects on human urethral fibroblasts are unknown. This study evaluated the effects of fasudil on cellular proliferation, migration, apoptosis, and collagen synthesis in human fibroblasts derived from urethral scar tissues. Human urethral scar fibroblasts were cultured by explant and incubated for 24 h or 48 h with fasudil (12.5, 25, 50 µmol/L) with or without transforming growth factor β1 (TGF-β1, 10 ng/mL), or left untreated (control)...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28385010/coactosin-like-protein-1-inhibits-the-neuronal-migration-during-mouse-corticogenesis
#19
Guohong Li, Yupeng Yin, Jiong Chen, Yanle Fan, Juhong Ma, Yingxue Huang, Chen Chen, Pengxiu Dai, Shulin Chen, Shanting Zhao
Coactosin-like protein-1 (Cotl1), a member of the actin-depolymerizing factor (ADF)/cofilin family, was first purified from the soluble fraction of Dictyostelium discoideum cells. Neuronal migration requires cytoskeletal remodeling and actin regulation. Although Cotl1 strongly binds to F-actin, the role of Cotl1 in neuronal migration remains unknown. Here, we revealed that Cotl1 overexpression impaired the migration of both early- and late-born neurons during mouse corticogenesis. Moreover, Cotl1 overexpression delayed, rather than blocked, neuronal migration in late-born neurons...
April 6, 2017: Journal of Veterinary Science
https://www.readbyqxmd.com/read/28381571/discovery-of-novel-small-molecule-inhibitors-of-lim-domain-kinase-for-inhibiting-hiv-1
#20
Fei Yi, Jia Guo, Deemah Dabbagh, Mark Spear, Sijia He, Kylene Kehn-Hall, Jacque Fontenot, Yan Yin, Mathieu Bibian, Chul Min Park, Ke Zheng, HaJeung Park, Veronica Soloveva, Dima Gharaibeh, Cary Retterer, Rouzbeh Zamani, Margaret L Pitt, John Naughton, Yongjun Jiang, Hong Shang, Ramin M Hakami, Binhua Ling, John A T Young, Sina Bavari, Xuehua Xu, Yangbo Feng, Yuntao Wu
A dynamic actin cytoskeleton is necessary for viral entry, intracellular migration, and virion release. For HIV-1 infection, during entry, the virus triggers early actin activity through hijacking chemokine coreceptor signaling which activates a host dependency factor cofilin and its kinase, the LIM domain kinase (LIMK). Although knockdown of human LIMK1 with shRNA inhibits HIV infection, no specific small molecule inhibitor of LIMK was available. Here we describe the design and discovery of novel classes of small molecule inhibitors of LIMK for inhibiting HIV infection...
April 5, 2017: Journal of Virology
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