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31.
The long range movements of membrane-bound ligands into surface caps and into the pseudopods of phagocytizing cells, the uropods of motile cells and the cleavage furrow of dividing cells appear to be analogous processes. A common mechanism to explain these movements must take into account several new and central observations: ligand-receptor complexes can migrate to regions of existing microfilament accumulation; laser photobleaching studies with fluorescent Con A indicate that ligand-receptor movement occurs unidirectionally; video computer analyses of Con A redistribution show that movement may exceed the maximum rates measured for protein diffusion in membranes. These observations are not consistent with models in which ligand-receptor movement occurs by diffusion or by direct interaction with contractile microfilaments. However, they can be satisfied by a new model that proposes the entrainment of selected membrane determinants on membrane waves directed towards regions such as caps, pseudopodia, uropods or cleavage furrow. These oriented waves are initiated by tension due to asymmetric microfilamentmembrane interaction. 相似文献
32.
Control of cell volume in the J774 macrophage by microtubule disassembly and cyclic AMP 总被引:8,自引:5,他引:3 下载免费PDF全文
We have explored the possibilities that cell volume is regulated by the status of microtubule assembly and cyclic AMP metabolism and may be coordinated with shape change. Treatment of J774.2 mouse macrophages with colchicine caused rapid microtubule disassembly and was associated with a striking increase (from 15-20 to more than 90 percent) in the proportion of cells with a large protuberance at one pole. This provided a simple experimental system in which shape changes occurred in virtually an entire cell population in suspension. Parallel changes in cell volume could then be quantified by isotope dilution techniques. We found that the shape change caused by colchicine was accompanied by a decrease in cell volume of approximately 20 percent. Nocodozole, but not lumicolchicine, caused identical changes in both cell shape and cell volume. The volume loss was not due to cell lysis nor to inhibition of pinocytosis. The mechanism of volume loss was also examined. Colchicine induced a small but reproducible increase in activity of the ouabain-sensitive Na(+), K(+)-dependent ATPase. However, inhibition of this enzyme/transport system by ouabain did not change cell volume nor did it block the colchicines-induced decrease in volume. One the other hand, SITS (4’acetamido, 4-isothiocyano 2,2’ disulfonic acid stilbene), an inhibitor of anion transport, inhibited the effects of colchicines, thus suggesting a role for an anion transport system in cell volume regulation. Because colchicine is known to activate adenylate cyclase in several systems and because cell shape changes are often induced by hormones that elevate cyclic AMP, we also examined the effects of cyclic AMP on cell volume. Agents that act to increase syclic AMP (cholera toxin, which activates adenylate cyclase; IBMX, and inhibitor of phosphodiesterase; and dibutyryl cyclic AMP) all caused a volume decrease comparable to that of colchicine. To define the effective metabolic pathway, we studied two mutants of J774.2, one deficient in adenylate cyclase and the other exhibiting markedly reduced activity of cyclic AMP-dependent protein kinase. Cholera toxin did not produce a volume change in either mutant. Cyclic AMP produced a decrease in the cyclase-deficient line comparable to that in wild type, but did not cause a volume change in the kinase- deficient line. This analysis established separate roles for cyclic AMP and colchicine. The volume decrease induced by cyclic AMP requires the action of a cyclic AMP-dependent protein kinase. Colchicine, on the other hand, induced a comparable volume change in both mutants and wild type, and thus does not require the kinase. 相似文献
33.
A carbamate herbicide causes microtubule and microfilament disruption and nuclear fragmentation in fibroblasts 总被引:1,自引:0,他引:1
Microtubule associated proteins (MAPs) are high molecular weight proteins that associate with microtubules during polymerization. This report describes a high molecular weight protein fraction with a molecular weight of approx. 290 000 from cultured mammalian fibroblasts that associates with polymerized rat brain tubulin. This protein(s), which is referred to as f-MAP, is enriched approx. 25-fold in a twice polymerized microtubules when compared with the original cell extract. Polymerization of rat brain extract in the presence of in vivo 32P-labeled fibroblast extract reveals the presence of a 32P-labeled protein in the polymerized pellet with the same electrophoretic mobility as f-MAP. The present study suggests that fibroblasts in culture contain a high molecular weight phosphoprotein with properties and a molecular weight very similar to the MAPs described in mammalian brain. 相似文献
34.
B.M. Fung David A. Wassil Dana L. Durham Robert W. Chesnut N.N. Durham K.D. Berlin 《Biochimica et Biophysica Acta (BBA)/General Subjects》1975,385(2)
The total water content, the amount of non-freezable water, and the Na+ and K+ contents in the gastrocnemius muscle of albino mice with and without a solid tumor were determined. The spin-lattice relaxation time (T1) for the water protons in the two kinds of muscle were measured at six resonance frequencies ranging from 4.5 to 60 MHz over the temperature range +37 to −65°C. Quantitatively calculated T1 values are given. The difference in T1 for the two types of muscle at temperatures above −5°C is attributed to the difference in the distribution ratio of water between hydration and free states, and bears no direct relation to the concentration of Na+. 相似文献
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Luise Ehlers Karen Bannert Sarah Rohde Peggy Berlin Johannes Reiner Mats Wiese Julia Doller Markus M. Lerch Ali A. Aghdassi Fatuma Meyer Luzia Valentini Ottavia Agrifoglio Cornelia C. Metges Georg Lamprecht Robert Jaster 《Journal of cellular and molecular medicine》2020,24(15):8304-8314
Muscle wasting represents a constant pathological feature of common chronic gastrointestinal diseases, including liver cirrhosis (LC), inflammatory bowel diseases (IBD), chronic pancreatitis (CP) and pancreatic cancer (PC), and is associated with increased morbidity and mortality. Recent clinical and experimental studies point to the existence of a gut‐skeletal muscle axis that is constituted by specific gut‐derived mediators which activate pro‐ and anti‐sarcopenic signalling pathways in skeletal muscle cells. A pathophysiological link between both organs is also provided by low‐grade systemic inflammation. Animal models of LC, IBD, CP and PC represent an important resource for mechanistic and preclinical studies on disease‐associated muscle wasting. They are also required to test and validate specific anti‐sarcopenic therapies prior to clinical application. In this article, we review frequently used rodent models of muscle wasting in the context of chronic gastrointestinal diseases, survey their specific advantages and limitations and discuss possibilities for further research activities in the field. We conclude that animal models of LC‐, IBD‐ and PC‐associated sarcopenia are an essential supplement to clinical studies because they may provide additional mechanistic insights and help to identify molecular targets for therapeutic interventions in humans. 相似文献
37.
Joe Carver Domingos Ng Michelle Zhou Peggy Ko Dejin Zhan Mandy Yim David Shaw Brad Snedecor Michael W. Laird Steven Lang Amy Shen Zhilan Hu 《Biotechnology progress》2020,36(4):e2967
Historically, therapeutic protein production in Chinese hamster ovary (CHO) cells has been accomplished by random integration (RI) of expression plasmids into the host cell genome. More recently, the development of targeted integration (TI) host cells has allowed for recombination of plasmid DNA into a predetermined genomic locus, eliminating one contributor to clone-to-clone variability. In this study, a TI host capable of simultaneously integrating two plasmids at the same genomic site was used to assess the effect of antibody heavy chain and light chain gene dosage on antibody productivity. Our results showed that increasing antibody gene copy number can increase specific productivity, but with diminishing returns as more antibody genes are added to the same TI locus. Random integration of additional antibody DNA copies in to a targeted integration cell line showed a further increase in specific productivity, suggesting that targeting additional genomic sites for gene integration may be beneficial. Additionally, the position of antibody genes in the two plasmids was observed to have a strong effect on antibody expression level. These findings shed light on vector design to maximize production of conventional antibodies or tune expression for proper assembly of complex or bispecific antibodies in a TI system. 相似文献
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Yumin Dai Liva Harinantenaina Peggy J. Brodie Chris Birkinshaw Richard Randrianaivo Wendy Applequist Michel Ratsimbason Vincent E. Rasamison Yongchun Shen Karen TenDyke David G. I. Kingston 《化学与生物多样性》2013,10(2):233-240
Investigation of the endemic Madagascan plant Nematostylis anthophylla (Rubiaceae) for antiproliferative activity against the A2780 ovarian cancer cell line led to the isolation of the known triterpene saponin randianin ( 1 ), and the two new bioactive triterpene saponins 2″‐O‐acetylrandianin ( 2 ) and 6″‐O‐acetylrandianin ( 3 ). The structures of the two new compounds were elucidated based on analysis of their 1D‐ and 2D‐NMR spectra, and mass spectrometric data. The three isolated triterpene saponins displayed moderate but selective antiproliferative activities, with IC50 values of 1.2, 1.7, and 2.2 μM , respectively, against the A2780 ovarian cancer, but only weak inhibitions of the proliferation of A2058 melanoma and the H522 lung cancer cell lines. 相似文献
40.
Chi Song Gary K. Chen Robert C. Millikan Christine B. Ambrosone Esther M. John Leslie Bernstein Wei Zheng Jennifer J. Hu Regina G. Ziegler Sarah Nyante Elisa V. Bandera Sue A. Ingles Michael F. Press Sandra L. Deming Jorge L. Rodriguez-Gil Stephen J. Chanock Peggy Wan Xin Sheng Loreall C. Pooler David J. Van Den Berg Loic Le Marchand Laurence N. Kolonel Brian E. Henderson Chris A. Haiman Daniel O. Stram 《PloS one》2013,8(2)
Genome-wide association studies (GWAS) simultaneously investigating hundreds of thousands of single nucleotide polymorphisms (SNP) have become a powerful tool in the investigation of new disease susceptibility loci. Haplotypes are sometimes thought to be superior to SNPs and are promising in genetic association analyses. The application of genome-wide haplotype analysis, however, is hindered by the complexity of haplotypes themselves and sophistication in computation. We systematically analyzed the haplotype effects for breast cancer risk among 5,761 African American women (3,016 cases and 2,745 controls) using a sliding window approach on the genome-wide scale. Three regions on chromosomes 1, 4 and 18 exhibited moderate haplotype effects. Furthermore, among 21 breast cancer susceptibility loci previously established in European populations, 10p15 and 14q24 are likely to harbor novel haplotype effects. We also proposed a heuristic of determining the significance level and the effective number of independent tests by the permutation analysis on chromosome 22 data. It suggests that the effective number was approximately half of the total (7,794 out of 15,645), thus the half number could serve as a quick reference to evaluating genome-wide significance if a similar sliding window approach of haplotype analysis is adopted in similar populations using similar genotype density. 相似文献