Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0344329 (collapse)
 28,634 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We present a comparative histopathological study of both acute and chronic human adenovirus pneumonia, with reference to the cellular and extracellular matrix components. Seventeen lungs from autopsied patients whose ages ranged from 2 to 60 months were studied. Adenovirus types 1, 2, 3, 5, and 7 were isolated from 15 patients with acute lung disease, and types 2 and 7 were isolated from the other two patients with chronic pulmonary illness. The results indicated the occurrence of two basic patterns of adenovirus interstitial pneumonia (1) classic pattern (acute), characterized by necrosis and degeneration and many type II pneumocytes with intranuclear inclusion bodies, which were positive for adenovirus DNA by in situ hybridization, and (2) proliferative or proliferative-productive pattern (chronic), which presented with diffuse pulmonary fibrosis and the interstitial proliferation of fibroblast-like cells, compatible with myofibroblasts (positive for vimentin and alpha smooth muscle actin), and increase in collagen types I and III, elastic fibers, and proteoglycans. Alveolar collapse appears to be an important pathogenetic mechanism in the development of this pattern.
 ...
PMID:Acute and chronic human adenovirus pneumonia: cellular and extracellular matrix components. 902 50

We report the presence of a novel filament system in goldfish xanthophores using a monoclonal antibody (A2) made against 40-70 kD proteins derived from cytoskeletal preparations. On Western blots, this antibody recognized a 45 kD protein in xanthophore cell extracts. In cells with dispersed pigment, immunofluorescence staining of xanthophores revealed a uniform distribution of A2-reactive filaments. In cells with aggregated pigment, these filaments assumed a distinctively radial orientation, such that filaments emanated from the central pigment mass (CPM). At the electron microscopic level, immunogold labeling identified a filament system with a diameter of 7 nm. Overall, the cellular distribution of A2-reactive filaments was distinctly different from that of the other known components of the cytoskeleton, such as intermediate filaments, actin filaments, and microtubules. A2-reactive filaments also appeared resistant to agents known to perturb the cytoskeleton such as cytochalasin B, which depolymerized the actin filaments. When xanthophores were treated with vinblastine, shown to depolymerize microtubules and induce the collapse of intermediate filaments (vimentin and keratin) in other cell types, no effect on the A2 filament distribution was observed. On the other hand, treatment with calyculin A, a phosphatase inhibitor, converted A2 filaments into a wavy bundles, the effect of which was completely reversible by the removal of the drug from culture medium. These novel properties of A2 filaments, together with their reorganization in response to pigment translocation suggest that A2 filaments might play a yet unidentified role in intracellular organelle transport in these cells.
 ...
PMID:Characterization of a novel filament system in goldfish xanthophores. 906 17

Research over the past few years on the function of intermediate filaments in cells in culture has not produced convincing results, because the key role of intermediate filaments is within tissues and at certain periods of development. Only recently the technique of gene knockout has been used to examine intermediate filaments in mice and has provided the first evidence that intermediate filaments are directly involved in cell resilience and the maintenance of tissue integrity. Knockout of the gene encoding keratin K8 is lethal in the embryo, and results in hepatic or intestinal lesions, while knockout of the K14 or K10 genes leads to rupture of stratified epithelia. Knockout of the gene encoding desmin causes the rupture of skeletal and cardiac muscle, and collapse of blood vessel walls. Knockout of the gene coding for GFAP leads to a loss of cerebral white matter, and knockout of the gene coding for vimentin causes degeneration of the cerebellar Purkinje cells. The results reveal the lack of compensation by another intermediate filament. Tissues without intermediate filaments fall apart; they are mechanically unstable, unable to resist physical stress, and this leads to cell degeneration. By maintaining the shape and plasticity of the cell, the intermediate filament network acts as an integrator within the cell space. The state of mechanical force imposed on a tissue or a cell can alter the shape of certain elements of the cytoskeleton and thus participate to the control of cell functions.
 ...
PMID:The importance of intermediate filaments in the adaptation of tissues to mechanical stress: evidence from gene knockout studies. 935 Nov 89

In order to study the dynamic behavior of intermediate filament networks in living cells, we have prepared constructs fusing green fluorescent protein to intermediate filament proteins. Vimentin fused to green fluorescent protein labeled the endogenous intermediate filament network. We generated stable SW13 and NIH3T3 cell lines that express an enhanced green fluorescent protein fused to the N-terminus of full-length vimentin. We were able to observe the dynamic behavior of the intermediate filament network in these cells for periods as long as 4 hours (images acquired every 2 minutes). In both cell lines, the vimentin network constantly moves in a wavy manner. In the NIH3T3 cells, we observed extension of individual vimentin filaments at the edge of the cell. This movement is dependent on microtubules, since the addition of nocodazole stopped the extension of the intermediate filaments. Injection of anti-IFA causes the redistribution or 'collapse' of intermediate filaments. We injected anti-IFA antibodies into NIH3T3 cells stably expressing green fluorescent protein fused to vimentin and found that individual intermediate filaments move slowly towards the perinuclear area without obvious disassembly. These results demonstrate that individual intermediate filaments are translocated during the collapse, rather than undergoing disassembly-induced redistribution. Injections of tubulin antibodies disrupt the interactions between intermediate filaments and stable microtubules and cause the collapse of the vimentin network showing that these interactions play an important role in keeping the intermediate filament network extended. The nocodazole inhibition of intermediate filament extension and the anti-IFA microinjection experiments are consistent with a model in which intermediate filaments exhibit an extended distribution when tethered to microtubules, but are translocated to the perinuclear area when these connections are severed.
 ...
PMID:Novel features of intermediate filament dynamics revealed by green fluorescent protein chimeras. 962 40

This study investigated in vitro the effect of therapeutic ultrasound (ULS) on smooth muscle cell (SMC) function as adhesion, migration and proliferation. Experiments were conducted on aortic SMC in culture. The LD50 was established (1.5 W for 15 s at a frequency of 20 kHz) and used as standard dose in all experiments. Control SMC and viable sonicated SMC were compared in each experiment. Migratory capacity decreased 2.4-fold after sonication and stayed reduced for up to 24 h. Adhesion capacity decreased 5.5-fold after ULS. The proliferative capacity was similar to that of nonsonicated SMC. Sonication was accompanied by the disorganization of alpha-SM actin fibers and diminished distribution of vinculin; tyrosinated alpha tubulin and vimentin appeared unaffected. These changes might be responsible for the observed inhibition of SMC adhesion and migration. Sonicated cells exhibited less lamellipodia, membrane collapse and bleb formation. The signal transduction cascade, which involves activation of the phospholipase-C pathway, was unaffected by ULS.
 ...
PMID:Ultrasound inhibits the adhesion and migration of smooth muscle cells in vitro. 969 75

The regulation of morphological changes in eukaryotic cells is a complex process involving major components of the cytoskeleton including actin microfilaments, microtubules, and intermediate filaments (IFs). The putative effector of RhoA, RhoA-binding kinase alpha (ROKalpha), is a serine/threonine kinase that has been implicated in the reorganization of actin filaments and in myosin contractility. Here, we show that ROKalpha also directly affects the structural integrity of IFs. Overexpression of active ROKalpha, like that of RhoA, caused the collapse of filamentous vimentin, a type III IF. A RhoA-binding-deficient, kinase-inactive ROKalpha inhibited the collapse of vimentin IFs induced by RhoA in HeLa cells. In vitro, ROKalpha bound and phosphorylated vimentin at its head-rod domain, thereby inhibiting the assembly of vimentin. ROKalpha colocalized predominantly with the filamentous vimentin network, which remained intact in serum-starved cells. Treatment of cells with vinblastine, a microtubule-disrupting agent, also resulted in filamentous vimentin collapse and concomitant ROKalpha translocation to the cell periphery. ROKalpha translocation did not occur when the vimentin network remained intact in vinblastine-treated cells at 4 degreesC or in the presence of the dominant-negative RhoAN19 mutant. Transient translocation of ROKalpha was also observed in cells subjected to heat shock, which caused the disassembly of the vimentin network. Thus, the translocation of ROKalpha to the cell periphery upon overexpression of RhoAV14 or growth factor treatment is associated with disassembly of vimentin IFs. These results indicate that Rho effectors known to act on microfilaments may be involved in regulating the assembly of IFs. Vimentin when phosphorylated also exhibits reduced affinity for the inactive ROKalpha. The translocation of ROKalpha from IFs to the cell periphery upon action by activated RhoA and ROKalpha suggests that ROKalpha may initiate its own cascade of activation.
 ...
PMID:RhoA-binding kinase alpha translocation is facilitated by the collapse of the vimentin intermediate filament network. 977 49

Posttranslationally modified forms of tubulin accumulate in the subset of stabilized microtubules (MTs) in cells but are not themselves involved in generating MT stability. We showed previously that stabilized, detyrosinated (Glu) MTs function to localize vimentin intermediate filaments (IFs) in fibroblasts. To determine whether tubulin detyrosination or MT stability is the critical element in the preferential association of IFs with Glu MTs, we microinjected nonpolymerizable Glu tubulin into cells. If detyrosination is critical, then soluble Glu tubulin should be a competitive inhibitor of the IF-MT interaction. Before microinjection, Glu tubulin was rendered nonpolymerizable and nontyrosinatable by treatment with iodoacetamide (IAA). Microinjected IAA-Glu tubulin disrupted the interaction of IFs with MTs, as assayed by the collapse of IFs to a perinuclear location, and had no detectable effect on the array of Glu or tyrosinated MTs in cells. Conversely, neither IAA-tyrosinated tubulin nor untreated Glu tubulin, which assembled into MTs, caused collapse of IFs when microinjected. The epitope on Glu tubulin responsible for interfering with the Glu MT-IF interaction was mapped by microinjecting tubulin fragments of alpha-tubulin. The 14-kDa C-terminal fragment of Glu tubulin (alpha-C Glu) induced IF collapse, whereas the 36-kDa N-terminal fragment of alpha-tubulin did not alter the IF array. The epitope required more than the detyrosination site at the C terminus, because a short peptide (a 7-mer) mimicking the C terminus of Glu tubulin did not disrupt the IF distribution. We previously showed that kinesin may mediate the interaction of Glu MTs and IFs. In this study we found that kinesin binding to MTs in vitro was inhibited by the same reagents (i.e., IAA-Glu tubulin and alpha-C Glu) that disrupted the IF-Glu MT interaction in vivo. These results demonstrate for the first time that tubulin detyrosination functions as a signal for the recruitment of IFs to MTs via a mechanism that is likely to involve kinesin.
 ...
PMID:Detyrosination of tubulin regulates the interaction of intermediate filaments with microtubules in vivo via a kinesin-dependent mechanism. 1019 60

We investigated the expression and the subcellular localization of S100A1 and S100B, two Ca(2+)-binding proteins of the EF-hand type, in replicating myoblasts and fused myotubes. Northern blot and reverse transcriptase-polymerase chain reaction analyses revealed the presence of S100A1 mRNA and S100B mRNA respectively, in myoblasts. Immunofluorescence and immunogold electron microscopy were used to localize individual proteins in myoblasts and myotubes. In the present report we document that: (1) in replicating myoblasts S100B is localized to intracellular membranes, including Golgi membranes, vimentin intermediate filaments (IFs) and microtubule (MT) structures; (2) in the same cells S100A1 is found associated with intracellular membranes; (3) following treatment of replicating myoblasts with colchicine, a fraction of S100B remains colocalized with bundled and collapsed vimentin IFs, whereas another fraction follows the destiny of endoplasmic membranes; (4) under the same conditions S100A1, like a fraction of S100B, follows the collapse of the endoplasmic reticulum around the nucleus; and (5) in fused myotubes S100A1 is found diffusely in the cytoplasm, whereas S100B is mostly found associated with vimentin IFs. These data suggest that in the skeletal myogenic cell line used in the present study S100A1 and S100B might share binding sites on or close to intracellular membranes, but display a significant degree of target specificity with respect of IFs and MTs. The results of these analyses suggest that expression of S100B in skeletal muscle cells may be developmentally regulated and lend support to the possibility that S100B might regulate the MT and IF dynamics.
 ...
PMID:Replicating myoblasts and fused myotubes express the calcium-regulated proteins S100A1 and S100B. 1032 76

The intermediate filament protein vimentin is a major phosphoprotein in mammalian fibroblasts, and reversible phosphorylation plays a key role in its dynamic rearrangement. Selective inhibition of type 2A but not type 1 protein phosphatases led to hyperphosphorylation and concomitant disassembly of vimentin, characterized by a collapse into bundles around the nucleus. We have analyzed the potential role of one of the major protein phosphatase 2A (PP2A) regulatory subunits, B55, in vimentin dephosphorylation. In mammalian fibroblasts, B55 protein was distributed ubiquitously throughout the cytoplasm with a fraction associated to vimentin. Specific depletion of B55 in living cells by antisense B55 RNA was accompanied by disassembly and increased phosphorylation of vimentin, as when type 2A phosphatases were inhibited using okadaic acid. The presence of B55 was a prerequisite for PP2A to efficiently dephosphorylate vimentin in vitro or to induce filament reassembly in situ. Both biochemical fractionation and immunofluorescence analysis of detergent-extracted cells revealed that fractions of PP2Ac, PR65, and B55 were tightly associated with vimentin. Furthermore, vimentin-associated PP2A catalytic subunit was displaced in B55-depleted cells. Taken together these data show that, in mammalian fibroblasts, the intermediate filament protein vimentin is dephosphorylated by PP2A, an event targeted by B55.
 ...
PMID:Vimentin dephosphorylation by protein phosphatase 2A is modulated by the targeting subunit B55. 1035 11

HSP27 and alphaB-crystallin are both members of the small heat shock protein family. alphaB-crystalllin has been proposed to modulate intermediate filaments and recently a mutation in alphaB-crystallin has been identified as the genetic basis of desmin related myopathy. This disease is characterised in its pathology by aggregates of intermediate filaments associated with alphaB-crystallin. Here we report that HSP27 like alphaB-crystallin is associated with glial fibrillary acidic protein and vimentin intermediate filament networks in unstressed U373MG astrocytoma cells. HSP27 is also associated with keratin filaments in MCF7 cells, indicating that this association is not restricted to a particular intermediate filament type. The association of sHSPs with both the soluble and filamentous intermediate filament fractions of U373 cells was demonstrated biochemically. Heat shock or drug treatments induced a co-collapse of intermediate filaments and associated small heat shock proteins. These data show that the presence of HSP27 or alphaB-crystallin could not prevent filament collapse and suggest that the purpose of this association is more than just filament binding. Indeed, in U373MG cells the intermediate filament association with small heat shock proteins is similar to that observed for another protein chaperone, HSC70. In order to discern the effect of different chaperone classes on intermediate filament network formation and maintenance, several in vitro assays were assessed. Of these, falling ball viscometry revealed a specific activity of small heat shock proteins compared to HSC70 that was apparently inactive in this assay. Intermediate filaments form a gel in the absence of small heat shock proteins. In contrast, inclusion of alphaB-crystallin or HSP27 prevented gel formation but not filament assembly. The transient transfection of GFAP into MCF7 cells was used to show that the induction of a completely separate network of intermediate filaments resulted in the specific association of the endogenous HSP27 with these new GFAP filaments. These data lead us to propose that one of the major functions of the association of small heat shock proteins with intermediate filaments is to help manage the interactions that occur between filaments in their cellular networks. This is achieved by protecting filaments against those non-covalent interactions that result when they come into very close proximity as seen from the viscosity experiments and which have the potential to induce intermediate filament aggregation as seen in some disease pathologies.
 ...
PMID:Intermediate filament interactions can be altered by HSP27 and alphaB-crystallin. 1036 40


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>