Cell health and cytoskeleton最新文献

{"title":"Alterations in cancer cell mechanical properties after fluid shear stress exposure: a micropipette aspiration study.","authors":"Venkat Keshav Chivukula,&nbsp;Benjamin L Krog,&nbsp;Jones T Nauseef,&nbsp;Michael D Henry,&nbsp;Sarah C Vigmostad","doi":"10.2147/CHC.S71852","DOIUrl":"https://doi.org/10.2147/CHC.S71852","url":null,"abstract":"<p><p>Over 90% of cancer deaths result not from primary tumor development, but from metastatic tumors that arise after cancer cells circulate to distal sites via the circulatory system. While it is known that metastasis is an inefficient process, the effect of hemodynamic parameters such as fluid shear stress (FSS) on the viability and efficacy of metastasis is not well understood. Recent work has shown that select cancer cells may be able to survive and possibly even adapt to FSS in vitro. The current research seeks to characterize the effect of FSS on the mechanical properties of suspended cancer cells in vitro. Nontransformed prostate epithelial cells (PrEC LH) and transformed prostate cancer cells (PC-3) were used in this study. The Young's modulus was determined using micropipette aspiration. We examined cells in suspension but not exposed to FSS (unsheared) and immediately after exposure to high (6,400 dyn/cm²) and low (510 dyn/cm²) FSS. The PrEC LH cells were ~140% stiffer than the PC-3 cells not exposed to FSS. Post-FSS exposure, there was an increase of ~77% in Young's modulus after exposure to high FSS and a ~47% increase in Young's modulus after exposure to low FSS for the PC-3 cells. There was no significant change in the Young's modulus of PrEC LH cells post-FSS exposure. Our findings indicate that cancer cells adapt to FSS, with an increased Young's modulus being one of the adaptive responses, and that this adaptation is specific only to PC-3 cells and is not seen in PrEC LH cells. Moreover, this adaptation appears to be graded in response to the magnitude of FSS experienced by the cancer cells. This is the first study investigating the effect of FSS on the mechanical properties of cancer cells in suspension, and may provide significant insights into the mechanism by which some select cancer cells may survive in the circulation, ultimately leading to metastasis at distal sites. Our findings suggest that biomechanical analysis of cancer cells could aid in identifying and diagnosing cancer in the future.</p>","PeriodicalId":72540,"journal":{"name":"Cell health and cytoskeleton","volume":"7 ","pages":"25-35"},"PeriodicalIF":0.0,"publicationDate":"2015-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CHC.S71852","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33247653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"THE RETINOBLASTOMA PROTEIN: A MASTER TUMOR SUPPRESSOR ACTS AS A LINK BETWEEN CELL CYCLE AND CELL ADHESION.","authors":"Brienne E. Engel, Cress Wd, Pedro G Santiago-Cardona","doi":"10.2147/CHC.S28079","DOIUrl":"https://doi.org/10.2147/CHC.S28079","url":null,"abstract":"RB1 was the first tumor suppressor gene discovered. Over four decades of work have revealed that the Rb protein (pRb) is a master regulator of biological pathways influencing virtually every aspect of intrinsic cell fate including cell growth, cell-cycle checkpoints, differentiation, senescence, self-renewal, replication, genomic stability and apoptosis. While these many processes may account for a significant portion of RB1's potency as a tumor suppressor, a small, but growing stream of evidence suggests that RB1 also significantly influences how a cell interacts with its environment, including cell-to-cell and cell-to-extracellular matrix interactions. This review will highlight pRb's role in the control of cell adhesion and how alterations in the adhesive properties of tumor cells may drive the deadly process of metastasis.","PeriodicalId":72540,"journal":{"name":"Cell health and cytoskeleton","volume":"7 1","pages":"1-10"},"PeriodicalIF":0.0,"publicationDate":"2014-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CHC.S28079","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68317418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Classification of axonal subtypes based on cytoskeletal components.","authors":"Ye Z Spector,&nbsp;Qi Zhao,&nbsp;Xiaopeng Zhao,&nbsp;William J Feuer,&nbsp;Portia Lynn Maravich,&nbsp;Xiang-Run Huang","doi":"10.2147/CHC.S57081","DOIUrl":"https://doi.org/10.2147/CHC.S57081","url":null,"abstract":"<p><strong>Background: </strong>Retinal ganglion cells are often classified into different subtypes according to their morphology or physiological functions. The axons of RGCs contain three major cytoskeletal components: actin filaments (F-actin); microtubules; and neurofilaments (NFs). The contents of these components vary among axons. Our objective was to classify axons into subtypes based on the contents of cytoskeletal components and study their distributions across the retina in normal rodent retinas.</p><p><strong>Methods: </strong>Whole-mounted retinas of female Wistar rats were stained with phalloidin to label F-actin, anti-β-tubulin monoclonal antibody to mark microtubules, and antineurofilament antibody to label NFs. A confocal laser scanning microscope was used to provide en face images of retinal nerve fiber bundles with a resolution of 0.24 μm/pixel. Staining intensity profiles across axons were obtained for each cytoskeletal component. Axonal subtypes were then determined from the relative contents, indicated by the staining intensity, of these components. Linear density was used to investigate topographical distribution of each subtype across the retina.</p><p><strong>Results: </strong>Normal axons could be classified into seven subtypes - FMN, FM, FN, and MN subtypes, (in which at least two or three cytoskeletal components were intensely stained), and F, M, and N subtypes, (in which only one cytoskeletal component was intensely stained within an axon). The FMN subtype was the most abundant subtype. There was no preferential distribution of subtypes around the optic nerve head. However, the densities of the axonal subtypes that contained NFs were found significantly different in the central and peripheral retinal regions. Axonal sizes were subtype-dependent.</p><p><strong>Conclusion: </strong>Axons of retinal ganglion cells can be classified into different subtypes, based on the contents of axonal cytoskeletal components. The classified subtypes will provide a new means to study selective damage of axonal ultrastructures in ocular neuropathic diseases.</p>","PeriodicalId":72540,"journal":{"name":"Cell health and cytoskeleton","volume":"6 ","pages":"1-10"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CHC.S57081","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9947341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New developments in C5a receptor signaling.","authors":"J Vidya Sarma,&nbsp;Peter A Ward","doi":"10.2147/CHC.S27233","DOIUrl":"https://doi.org/10.2147/CHC.S27233","url":null,"abstract":"<p><p>Complement activation usually results in the formation of complement fragment 5a (C5a) that interacts with its two receptors, C5aR and C5L2. These receptors belong to the rhodopsin family of G protein-coupled seven transmembrane-containing receptors. C5aR and C5L2 are expressed on/in a wide variety of cells and tissues. Interaction of C5a with C5aR leads to many pleiotropic effects, including the release of cytokines and chemokines and recruitment of inflammatory cells. In certain circumstances, C5a-C5aR interactions can also result in pathophysiological changes as seen in sepsis, rheumatoid arthritis, asthma, acute lung injury and ischemia-reperfusion injury. This overview of the C5a-C5aR interactions describes how such interactions facilitate the pivotal role the complement system plays in the host's innate and adaptive responses.</p>","PeriodicalId":72540,"journal":{"name":"Cell health and cytoskeleton","volume":"4 ","pages":"73-82"},"PeriodicalIF":0.0,"publicationDate":"2012-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CHC.S27233","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31349273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of nicotine on the mechanical properties of mesenchymal stem cells.","authors":"Juan P Ruiz,&nbsp;Daniel Pelaez,&nbsp;Janice Dias,&nbsp;Noël M Ziebarth,&nbsp;Herman S Cheung","doi":"10.2147/CHC.S24381","DOIUrl":"https://doi.org/10.2147/CHC.S24381","url":null,"abstract":"<p><p>PURPOSE: To measure the elasticity of the nucleus and cytoplasm of human mesenchymal stem cells (MSCs) as well as changes brought about by exposure to nicotine in vitro. METHODS: MSCs were synchronized to the G(0) stage of the cell cycle through serum deprivation techniques. The cells were then treated with medium containing nicotine (0.1 µM, 0.5 µM, and 1 µM). Atomic force microscopy was then used to measure the Young's modulus of both the nucleus and cytoplasm of these cells. RESULTS: For both unsynchronized and synchronized cells, the nucleus was softer than the cytoplasm, although this difference was not found to be statistically significant. The nucleus of cells treated with nicotine was significantly stiffer than the control for all concentrations. The cytoplasm was significantly stiffer in nicotine-treated cells than in control cells for the 0.5 µM and 1.0 µM concentrations only. CONCLUSIONS: The results of this study could suggest that nicotine affects the biophysical properties of human MSCs in a dose-dependent manner, which may render the cells less responsive to mechanoinduction and other physical stimuli.</p>","PeriodicalId":72540,"journal":{"name":"Cell health and cytoskeleton","volume":"4 ","pages":"29-35"},"PeriodicalIF":0.0,"publicationDate":"2012-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CHC.S24381","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30972938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of apoptosis-inducing factor, proline dehydrogenase, and NADPH oxidase in apoptosis and oxidative stress.","authors":"Sathish Kumar Natarajan,&nbsp;Donald F Becker","doi":"10.2147/CHC.S4955","DOIUrl":"https://doi.org/10.2147/CHC.S4955","url":null,"abstract":"<p><p>Flavoproteins catalyze a variety of reactions utilizing flavin mononucleotide or flavin adenine dinucleotide as cofactors. The oxidoreductase properties of flavoenzymes implicate them in redox homeostasis, oxidative stress, and various cellular processes, including programmed cell death. Here we explore three critical flavoproteins involved in apoptosis and redox signaling, ie, apoptosis-inducing factor (AIF), proline dehydrogenase, and NADPH oxidase. These proteins have diverse biochemical functions and influence apoptotic signaling by unique mechanisms. The role of AIF in apoptotic signaling is two-fold, with AIF changing intracellular location from the inner mitochondrial membrane space to the nucleus upon exposure of cells to apoptotic stimuli. In the mitochondria, AIF enhances mitochondrial bioenergetics and complex I activity/assembly to help maintain proper cellular redox homeostasis. After translocating to the nucleus, AIF forms a chromatin degrading complex with other proteins, such as cyclophilin A. AIF translocation from the mitochondria to the nucleus is triggered by oxidative stress, implicating AIF as a mitochondrial redox sensor. Proline dehydrogenase is a membrane-associated flavoenzyme in the mitochondrion that catalyzes the rate-limiting step of proline oxidation. Upregulation of proline dehydrogenase by the tumor suppressor, p53, leads to enhanced mitochondrial reactive oxygen species that induce the intrinsic apoptotic pathway. NADPH oxidases are a group of enzymes that generate reactive oxygen species for oxidative stress and signaling purposes. Upon activation, NADPH oxidase 2 generates a burst of superoxide in neutrophils that leads to killing of microbes during phagocytosis. NADPH oxidases also participate in redox signaling that involves hydrogen peroxide-mediated activation of different pathways regulating cell proliferation and cell death. Potential therapeutic strategies for each enzyme are also highlighted.</p>","PeriodicalId":72540,"journal":{"name":"Cell health and cytoskeleton","volume":"2012 4","pages":"11-27"},"PeriodicalIF":0.0,"publicationDate":"2012-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CHC.S4955","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30623838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"N-glycosylation status of E-cadherin controls cytoskeletal dynamics through the organization of distinct β-catenin- and γ-catenin-containing AJs.","authors":"Basem T Jamal,&nbsp;Mihai Nita-Lazar,&nbsp;Zhennan Gao,&nbsp;Bakr Amin,&nbsp;Janice Walker,&nbsp;Maria A Kukuruzinska","doi":"10.2147/chc.s5965","DOIUrl":"https://doi.org/10.2147/chc.s5965","url":null,"abstract":"N-glycosylation of E-cadherin has been shown to inhibit cell-cell adhesion. Specifically, our recent studies have provided evidence that the reduction of E-cadherin N-glycosylation promoted the recruitment of stabilizing components, vinculin and serine/threonine protein phosphatase 2A (PP2A), to adherens junctions (AJs) and enhanced the association of AJs with the actin cytoskeleton. Here, we examined the details of how N-glycosylation of E-cadherin affected the molecular organization of AJs and their cytoskeletal interactions. Using the hypoglycosylated E-cadherin variant, V13, we show that V13/β-catenin complexes preferentially interacted with PP2A and with the microtubule motor protein dynein. This correlated with dephosphorylation of the microtubule-associated protein tau, suggesting that increased association of PP2A with V13-containing AJs promoted their tethering to microtubules. On the other hand V13/γ-catenin complexes associated more with vinculin, suggesting that they mediated the interaction of AJs with the actin cytoskeleton. N-glycosylation driven changes in the molecular organization of AJs were physiologically significant because transfection of V13 into A253 cancer cells, lacking both mature AJs and tight junctions (TJs), promoted the formation of stable AJs and enhanced the function of TJs to a greater extent than wild-type E-cadherin. These studies provide the first mechanistic insights into how N-glycosylation of E-cadherin drives changes in AJ composition through the assembly of distinct β-catenin- and γ-catenin-containing scaffolds that impact the interaction with different cytoskeletal components.","PeriodicalId":72540,"journal":{"name":"Cell health and cytoskeleton","volume":"2009 1","pages":"67-80"},"PeriodicalIF":0.0,"publicationDate":"2009-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/chc.s5965","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29016589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endothelial contractile cytoskeleton and microvascular permeability.","authors":"Qiang Shen,&nbsp;Mack H Wu,&nbsp;Sarah Y Yuan","doi":"10.2147/chc.s5118","DOIUrl":"https://doi.org/10.2147/chc.s5118","url":null,"abstract":"<p><p>Microvascular barrier dysfunction represents a significant problem in clinical conditions associated with trauma, burn, sepsis, acute respiratory distress syndrome, ischemia-reperfusion injury, and diabetic retinopathy. An important cellular mechanism underlying microvascular leakage is the generation of contractile force from the endothelial cytoskeleton, which counteracts cell-cell and cell-matrix adhesions leading to paracellular hyperpermeability. In this review, we present recent experimental evidence supporting the critical role of MLCK-activated, RhoA/ROCK-regulated contractile cytoskeleton in endothelial permeability response to inflammatory and thrombotic stimuli arising from thermal injury, activated neutrophils, vascular endothelial growth factor, and fibrinogen degradation products. Further understanding the molecular basis of microvascular barrier structure and function would contribute to the development of novel therapeutic targets for treating circulatory disorders and vascular injury.</p>","PeriodicalId":72540,"journal":{"name":"Cell health and cytoskeleton","volume":"2009 1","pages":"43-50"},"PeriodicalIF":0.0,"publicationDate":"2009-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/chc.s5118","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29307884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HSP20 phosphorylation and airway smooth muscle relaxation.","authors":"Mariam Ba,&nbsp;Cherie A Singer,&nbsp;Manoj Tyagi,&nbsp;Colleen Brophy,&nbsp;Josh E Baker,&nbsp;Christine Cremo,&nbsp;Andrew Halayko,&nbsp;William T Gerthoffer","doi":"10.2147/chc.s5783","DOIUrl":"https://doi.org/10.2147/chc.s5783","url":null,"abstract":"<p><p>HSP20 (HSPB6) is a small heat shock protein expressed in smooth muscles that is hypothesized to inhibit contraction when phosphorylated by cAMP-dependent protein kinase. To investigate this hypothesis in airway smooth muscle (ASM) we showed that HSP20 was constitutively expressed as well as being inducible in cultured hASM cells by treatment with 1 μM isoproterenol or 10 μM salmeterol. In contrast, a mixture of proinflammatory mediators (interleukin-1β, tumor necrosis factor α, and interferon γ) inhibited expression of HSP20 by about 50% in 48 hours. To determine whether phosphorylation of HSP20 is sufficient to induce relaxation, canine tracheal smooth muscle was treated with a cell permeant phosphopeptide that mimics the phosphorylation of HSP20. The HSP20 phosphopeptide antagonized carbachol-induced contraction by 60% with no change in myosin light chain phosphorylation. Recombinant full length HSP20 inhibited skeletal actin binding to smooth muscle myosin subfragment 1 (S1), and recombinant cell permeant TAT-HSP20 S16D mutant reduced F-actin filaments in cultured hASM cells. Carbachol stimulation of canine tracheal smooth muscle tissue caused redistribution of HSP20 from large macromolecular complexes (200-500 kDa) to smaller complexes (<60 kDa). The results are consistent with HSP20 expression and macromolecular structure being dynamically regulated in airway smooth muscle. HSP20 is upregulated by beta agonists and downregulated by proinflammatory cytokines. HSP20 is phosphorylated in vivo in a cAMP-dependent manner and the phosphorylated form promotes airway smooth muscle relaxation, possibly through depolymerization of F-actin as well as inhibition of myosin binding to actin.</p>","PeriodicalId":72540,"journal":{"name":"Cell health and cytoskeleton","volume":"2009 1","pages":"27-42"},"PeriodicalIF":0.0,"publicationDate":"2009-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/chc.s5783","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29947793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}