PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Cell Growth Processes”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

Effect of proline rich domain of an RNA-binding protein Sam68 in cell growth process, death and B cell signal transduction.

BACKGROUND: Sam68 plays an important role as a multiple functional RNA binding nuclear protein in cell cycle progress, RNA usage, signal transduction, and tyrosine phosphorylation by Src during mitosis. However, its precise impact on these essential cellular functions remains unclear. The purpose of this study is to further elucidate Sam68 functions in RNA metabolism, signal transduction regulation of cell growth and cell proliferation in DT40 cell line. METHODS: By using gene targeting method, we isolated a mutation form of Sam68 in DT40 cells and described its effect on cell growth process and signal transduction. Southern, Northern, and Western blot, phosphorylation and flow-cytometric analyses were performed to investigate the Sam68 functions. RESULTS: A slower growth rate (2.1 hours growth elongation) and longer S phase (1.7 hours elongation) was observed in the Sam68 mutant cells. Serum depletion resulted in increased amounts of dead cells, and expansion of S phase in mutant cells. Upon B cell cross-linking, the maximal level of tyrosine phosphorylation on BLNK was observed to be significantly lower in mutant cells. CONCLUSIONS: The proline rich domain of Sam68 is involved in cell growth control by modulating the function of mRNAs in S phase or earlier and the functions as an adaptor molecule in B cell signal transduction pathways.

Adaptor Proteins, Signal Transducing↗

Three-dimensional reconstruction of pulmonary arteries in plexiform pulmonary hypertension using cell-specific markers. Evidence for a dynamic and heterogeneous process of pulmonary endothelial cell growth.

The plexiform lesions of severe pulmonary hypertension (PH) are complex vascular structures composed primarily of endothelial cells. In this study, we use immunohistochemical markers to identify the various cell layers of pulmonary vessels and to identify different endothelial cell phenotypes in pulmonary arteries affected by severe PH. Our computerized three-dimensional reconstructions of nine vessels in five patients with severe PH demonstrate that plexiform (n = 14) and concentric-obliterative (n = 6) lesions occur distal to branch points of small pulmonary arteries. And, whereas plexiform lesions occur as solitary lesions, concentric-obliterative lesions appear to be only associated with, and proximal to, plexiform structures. The endothelial cells of plexiform lesions express intensely and uniformly the vascular endothelial growth factor (VEGF) receptor KDR and segregate phenotypically into cyclin-kinase inhibitor p27/kip1-negative cells in the central core of the plexiform lesion and p27/kip1-positive cells in peripheral areas adjacent to incipient blood vessel formation. Using immunohistochemistry and three-dimensional reconstruction techniques, we show that plexiform lesions are dynamic vascular structures characterized by at least two endothelial cell phenotypes. Plexiform arteriopathy is not merely an end stage or postthrombotic change--it may represent one stage in an ongoing, angiogenic endothelial cell growth process.

Actins↗

Membrane specializations of neuritic growth cones in vivo: a quantitative IMP analysis.

The internal structure of the membranes of axonal and Schwann cell growth processes was examined by freeze-fracture in the growing olfactory nerve, a simple in vivo system consisting of a homogeneous neuronal population. Excision of the mature nerve of adult bullfrogs provides well-synchronized primary neuritic outgrowth that is highly enriched in growth cones at its distalmost segment. The extreme uniformity of olfactory axons in terms of their diameter and their intramembrane particle (IMP) composition permits clear identification of the cellular origin of the growth cone structures observed in replicas. In vivo, growth cones of the olfactory nerve appear as irregularly shaped enlargements of the distal tip; filopodia are only infrequently exposed by the fracture plane. Axonal and Schwann cell growth cones are distinguished by 1) the larger size of the Schwann cell growth cone and the smaller diameter of its attached processes, and 2) the distinct differences in IMP composition of Schwann cell and axonal growth cones and cell processes. Schwann cell growth cones display a uniformly high IMP density on their P-face leaflet, with the exception of circumscribed moundlike protrusions that are relatively free of IMPs. In contrast, axonal growth cones display sharp regional variation in IMP density on their P-face: broad regions almost devoid of IMPs are interspersed with zones of high IMP density. Cytotic profiles occur within high IMP density zones located, most often, at the base of the axonal growth cone. A comparison of IMP size histograms of both high and low-density regions of axonal growth cones and that of the neighboring distal shaft of the axon indicates a strict partitioning of membrane components between these two regions. The IMP profile of the axonal growth cone, notable for its relative enrichment in large-diameter particles, suggests that IMP components of the growth cone are delivered to the distal tip by a mechanism that is distinct from the lateral diffusion process described for particles of the growing axon's shaft [cf. Small and Pfenninger, 1984]. The IMP profile of the concave P-face leaflet of the internal vesicles found clustered at the base of the growth cone is more similar in composition to the profile of the neuronal shaft than that of the growth cone.

Animals↗

Structural and functional compartmentalization in pollen tubes.

Eukaryotic cellular functions are achieved by concerted activities in the cytosol and functions compartmentalized in the nucleus and other membrane-bound organelles. Moreover, the cytosol and nucleoplasm are populated with mega molecular ensembles that are specialized for different metabolic and biochemical processes. Pollen tubes are unique plant cells with a dramatic growth polarity. Tube growth is restricted to the tip and is supported by a polarized cytoplasmic organization. The apical region of elongating pollen tubes is a domain occupied exclusively by transport vesicles to support the secretion and endocytic activity needed for the rapid cell expansion at the apex. Larger organelles are predominantly segregated to the cytoplasm distal to the subapical region. Underlying the organelle compartmentalization is an elaborate actin cytoskeleton with distinct structural and dynamics properties at the tip, in the subapical region, and in the cytoplasm subtending it. Cytoplasmic domains with differential ionic conditions and spatially restricted localization of molecules in pollen tubes may also be important for regulating the polar cell growth process. The polarized cellular organization in pollen tubes drives an extremely efficient cell growth process that is responsive to extracellular signals, including directional cues. It may be an amplified framework of the cytoplasmic architecture that supports growth in other plant cell types that involves considerably more subtle and transient differential cell expansion.

Cell Compartmentation↗

Point mutation at single tyrosine residue of novel oncogene NOK abrogates tumorigenesis in nude mice.

Receptor protein-tyrosine kinases (RPTKs) are tightly regulated during normal cellular processes including cell growth, differentiation, and metabolism. Recently, a RPTK-like molecule named novel oncogene with kinase-domain (NOK) has been cloned and characterized. Overexpression of NOK caused severe cellular transformation as well as tumorigenesis and metastasis in nude mice. In the current study, we generated two tyrosine-->phenylalanine (Y-->F) point mutations (Y327F and Y356F) within the endodomain of NOK that are well conserved in many RPTK subfamilies and are the potential tyrosine phosphorylation sites important for major intracellular signaling. Using BaF3 cells stably expressing the ectodomain of mouse erythropoietin receptor, and the transmembrane and endodomain of NOK (BaF3-E/N), we were able to show that point mutations at either Y327 or Y356 dramatically blocked cellular transformation by NOK as examined by colony formation and cellular DNA synthesis. In addition, tumorigenesis induced by BaF3-E/N was completely abrogated upon the introduction of either single mutation. Importantly, signaling studies revealed that the activation of extracellular signal-regulated kinase was inhibited by Y356F and was significantly reduced by Y327F. Both mutations significantly impaired Akt phosphorylation. Interestingly, both mutations did not affect the kinase activity of NOK. Moreover, apoptotic analysis revealed that both mutations accelerated cell death by activating caspase-3-mediated pathways. Thus, our study shows that these potential tyrosine phosphorylation sites may play critical roles in NOK-mediated tumorigenesis both in vitro and in vivo.

Animals↗

Regional differences in in vitro growth of neural cell processes during development.

Primary cell cultures from cerebral cortex, striatum and ventral mesencephalon obtained from rat fetal (embryonic day 17, E17) or postnatal (day 2, PN2) donors were grown either in media conditioned by subcultured astroglia from the same regions, an artificial trophic medium, normal human amniotic fluid, or in normal human cerebrospinal fluid. To estimate the presence of neuronal-like and non-neuronal cells, cell morphology and immunocytochemistry against microtubule-associated proteins and beta-tubulin were taken into consideration. The percentage of emitting neural cells and length of cell processes were determined after 24 hr in culture. Growth of cell processes in neuronal and non-neuronal cells from prenatal striatum was minimal compared with that in cerebral cortex and ventral mesencephalon, regardless of the culture condition. Nerve growth factor, basic fibroblast growth factor or epidermal growth factor did not significantly modify cell growth in E17 cultures, except for epidermal growth factor, which reduced the number of emitting cells in striatal cultures and increased it in cerebral cortex ones. Cultures derived from postnatal striatum showed a significant increase in neurite length when grown in an astroglial conditioned medium as compared to cultures derived from prenatal (E17) striatum. Results suggest significant regional differences in the brain regarding growth of cell processes at age E17, and reversal of striatal ability to grow cell processes by postnatal day 2. Reduced growth of cell processes showed by E17 striatum cultures was rather independent of the culture media. This fact could suggest that such early regional differences would depend on characteristics of sublineages present at this developmental stage, which would modulate the organization of regional neuropils. The restricted growth of cell processes in cultures from E17 striatum, no longer present in postnatal striatum, suggests that inputs to the striatum may modify expression of cell lineages at later stages of development.

Amniotic Fluid↗

The role of RbfA in 16S rRNA processing and cell growth at low temperature in Escherichia coli.

RbfA, a 30S ribosome-binding factor, is a multicopy suppressor of a cold-sensitive C23U mutation of the 16S rRNA and is required for efficient processing of the 16S rRNA. At 37 degrees C, DeltarbfA cells show accumulation of ribosomal subunits and 16S rRNA precursor with a significantly reduced polysome profile in comparison with wild-type cells. RbfA is also a cold-shock protein essential for Escherichia coli cells to adapt to low temperature. In this study, we examined its association with the ribosome and its role in 16S rRNA processing and ribosome profiles at low temperature. In wild-type cells, following cold shock at 15 degrees C, the amount of free RbfA remained largely stable, while that of its 30S subunit-associated form became several times greater than that at 37 degrees C and a larger fraction of total 30S subunits was detected to be RbfA-containing. In DeltarbfA cells, the pre-16S rRNA amount increased after cold shock with a concomitant reduction of the mature 16S rRNA amount and the formation of polysomes was further reduced. A closer examination revealed that 30S ribosomal subunits of DeltarbfA cells at low temperature contained primarily pre-16S rRNA and little mature 16S rRNA. Our results indicate that the cold sensitivity of DeltarbfA cells is directly related to their lack of translation initiation-capable 30S subunits containing mature 16S rRNA at low temperature. Importantly, when the C-terminal 25 residue sequence was deleted, the resulting RbfADelta25 lost the abilities to stably associate with the 30S subunit and to suppress the dominant-negative, cold-sensitive phenotype of the C23U mutation in 16S rRNA but was able to suppress the 16S rRNA processing defect and the cold-sensitive phenotype of the DeltarbfA cells, suggesting that RbfA may interact with the 30S ribosome at more than one site or function in more than one fashion in assisting the 16S rRNA maturation at low temperature.

Cell Division↗

Overexpression of an Arabidopsis formin stimulates supernumerary actin cable formation from pollen tube cell membrane.

Formins, actin-nucleating proteins that stimulate the de novo polymerization of actin filaments, are important for diverse cellular and developmental processes, especially those dependent on polarity establishment. A subset of plant formins, referred to as group I, is distinct from formins from other species in having evolved a unique N-terminal structure with a signal peptide, a Pro-rich, potentially glycosylated extracellular domain, and a transmembrane domain. We show here that overexpression of the Arabidopsis formin AFH1 in pollen tubes induces the formation of arrays of actin cables that project into the cytoplasm from the cell membrane and that its N-terminal structure targets AFH1 to the cell membrane. Pollen tube elongation is a polar cell growth process dependent on an active and tightly regulated actin cytoskeleton. Slight increases in AFH1 stimulate growth, but its overexpression induces tube broadening, growth depolarization, and growth arrest in transformed pollen tubes. These results suggest that AFH1-regulated actin polymerization is important for the polar pollen cell growth process. Moreover, severe membrane deformation was observed in the apical region of tip-expanded, AFH1-overexpressing pollen tubes in which an abundance of AFH1-induced membrane-associated actin cables was evident. These observations suggest that regulated AFH1 activity at the cell surface is important for maintaining tip-focused cell membrane expansion for the polar extension of pollen tubes. The cell surface-located group-I formins may play the integrin-analogous role as mediators of external stimuli to the actin cytoskeleton, and AFH1 could be important for mediating extracellular signals from female tissues to elicit the proper pollen tube growth response during pollination.

Actins↗

Trafficking of nuclear heparin-binding epidermal growth factor-like growth factor into an epidermal growth factor receptor-dependent autocrine loop in response to oxidative stress.

Heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) accumulates in the nucleus in aggressive transitional cell carcinoma (TCC) cells and this histologic feature is a marker of poor prognosis in human bladder cancer tissues. Here we report that HB-EGF can be exported from the nucleus during stimulated processing and secretion of the growth factor. Production of reactive oxygen species (ROS) resulted in mobilization of the HB-EGF precursor, proHB-EGF, from the nucleus of TCCSUP bladder cancer cells to a detergent-resistant membrane compartment, where the growth factor was cleaved by a metalloproteinase-mediated mechanism and shed into the extracellular space. Inhibition of nuclear export suppressed HB-EGF shedding. Production of ROS resulted in EGF receptor (EGFR) and Akt1 phosphorylation in HB-EGF-expressing cells. HB-EGF also stimulated cell proliferation and conferred cytoprotection when cells were challenged with cisplatin. These findings show that the nucleus can serve as an intracellular reservoir for a secreted EGFR ligand and, thus, can contribute to an autocrine loop leading to cell proliferation and protection from apoptotic stimuli.

Active Transport, Cell Nucleus↗

Epidermal cell cycle and region-specific growth during segment development in Artemia.

During larval development in instar IV brine shrimp, segment 1 grew by cell replication and cell differentiation. Cell cycle analysis revealed that the cell cycle was synchronized with the molt cycle. Mitosis occurred late in the instar and S phase began at hr 6 of the following instar. Three populations of cells comprised the dorsal integument. The medial-dorsal region did not grow. Cell enlargement occurred in the dorsal-lateral population while cell replication took place in the lateral population. The limb bud (ventral surface) grew in width by replication in the distal population, and in height by enlargement of the general epidermal cells in the proximal population. Expansion of each region of the integument was proportional to the cell growth in that region. Moreover, both growth processes were dependent on the level of nutrients and were enhanced by diets enriched in polyunsaturated fatty acids. A nutrient-dependent growth control point occurred in the G1 period. The commitment to replication and differentiation occurred by hr 2 of instar IV. The findings show that integumental growth is a result of region-specific cell growth processes which are controlled by nutrients during the G1 period.

Animal Nutritional Physiological Phenomena↗

Human papillomavirus-16 E6/E7 transfected retinal cell line expresses the Müller cell phenotype.

The introduction of viral transforming genes into mammalian cells has been used in establishing cultures of unlimited lifespan. Although Müller cells, the predominant glial cells in the mammalian retina, have been isolated using a variety of techniques, most of these cultures have limited capacity for cell division and are often contaminated by other cell types especially astrocytes, endothelial cells and microglial cells. We have established pure cultures of retinal cells which express Müller cell characteristics and exhibit unlimited growth in vitro. We now report the techniques involved in the propagation and characterization of these cultures. Mixed retinal cultures isolated from dystrophic rat retinas were infected with defective retroviruses coding for human papillomavirus (HPV) type 16 E6 and E7 proteins. The disabled viral constructs also contained the neomycin gene allowing selection of the cultures using Geneticin, a neomycin analogue. Pure cultures were then obtained from Geneticin-selected populations by limiting end-dilution techniques. The expression of the HPV-16 E6/E7 genes in the transfected cell line was established using an HPV-16 E6/E7 PCR product to probe Northern blots. Cloned cells were found to be highly reactive for Müller cell markers including S-100, carbonic anhydrase-C, cellular retinaldehyde binding protein, and glial fibrillary acidic protein but not for glutamine synthetase. Ultrastructural studies showed stacks of cells with long elaborate processes, short microvilli, coated pits, cytoplasmic filaments, abundant perinuclear rough endoplasmic reticulum, and smooth endoplasmic reticulum extending to the cell processes. Growth patterns of late passage cells (> 50 passages) showed a lag phase of 48 hr followed by exponential growth extending past visual confluence at day 5. Since the cultures have undergone more than 240 population doublings, they can be characterized as a continuous cell line with unlimited lifespan. The HPV-16 E6/E7 transfected Müller cell line may prove useful in studies requiring abundant and pure cultures of Müller cells.

Animals↗

Regeneration and maturation of daughter cell walls in the autospore-forming green alga Chlorella vulgaris (Chlorophyta, Trebouxiophyceae).

Cell-wall synthesis in Chlorella vulgaris, an autospore-forming alga, was observed using the cell wall-specific fluorescent dye Fluostain I. The observation suggested two clearly distinguishable stages in cell-wall synthesis: moderate synthesis during the cell-growth process and rapid synthesis at the cell-division stage. We used electron microscopy to examine the structural changes that occurred with growth in the premature daughter cell wall during the cell-growth and cell-division phases. The cell began to synthesize a new daughter cell wall shortly after its release from the autosporangium. A very thin daughter cell wall, with a thickness of about 2 nm, was formed inside the mother cell wall and completely enveloped the outer surface of the plasma membrane of the cell. The daughter cell wall gradually increased in thickness from 2 to 3.8 nm. During the protoplast-division phase in the cell-division stage, the daughter cell wall expanded on the surface of the invaginating plasma membrane of the cleavage furrow, accompanied by active synthesis of the cell wall, which increased in thickness from 3.8 to 6.1 nm. The daughter cell matured into an autospore while completely enclosed by its own thickening (from 6.1 to 17 nm) wall. Finally, the released daughter cell was enclosed by its own cell wall after the mother cell wall burst. The daughter cell with mature wall thickness (17-21 nm) emerged as a small, but complete, autospore.

Cell Cycle↗

Relationship between cell proliferation and transition to elongation in plant roots.

Relationship between two main growth processes, cell proliferation and elongation, is reviewed. In literature, meristem and elongation zones are discriminated according to: increase in relative growth rate, change in cell shape, cessation of mitoses, and change in cell structure, vacuolation in particular. Relative growth rate is almost constant along the meristem and increases sharply in the course of cell transition to elongation. The transition of cells to elongation cannot be considered as a continuation of meristematic growth after the cessation of divisions. The most valid criterion of the cell transition to elongation is a sharp rise in relative growth rate, ratherthan change in cell shape (form factor). In the growing roottip, there aretwo regions of more active accumulation of proteins. The first is associated with the fastest cell proliferation while the second corresponds to enhanced cell elongation. The results of experiments with X-irradiation and cytostatic drugs suggest that cell transition to elongation is independent of cell proliferation and is regulated by the processes determining the life-span of cells in the meristem. The rate of cell transition to elongation is controlled by the processes determining both the life-span of cells in the meristem and the rate of cell proliferation. For most meristematic cells, the life-span of most cells in the meristem remains unchanged in treated roots. Thus, if cell proliferation and transition to elongation are regulated independently, any retardation of cell proliferation will automatically result in deceleration of the cell transition to elongation. Cell kinetics in roots is similar to that in some mammalian tissues capable of long-term proliferation.

Cell Division↗