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)

Prosomes are small ribonucleoprotein (RNP) particles of unique morphology in the electron microscope but of variable protein and RNA composition, depending on the differentiation state of the cells studied. They were initially observed as subcomplexes of untranslated mRNP. In previous studies, we found that prosomes are associated to the intermediate filaments (IF) of cytokeratin type in HeLa and PtK1 cells. Here we have studied in detail the association of prosomal antigens with the IF networks in PtK1 cells. Contrary to our earlier conclusions, in these cells the vimentin fibers also carry prosomes which, thus, distribute in between the two types of networks. During the selective collapse of the IF induced by acrylamide, and upon recovery after the withdrawal of the drug, no dissociation of the prosome and IF networks of cytokeratin- and vimentin-type could be observed. These data show that even in a dynamic situation, prosome and IF antigens do not dissociate, indicating strongly that they are located on one and the same structure. Furthermore, the differential distribution of specific prosomal antigens between both types of intermediate filament networks indicates that prosomes do not ubiquitously populate the intermediate filaments but occupy subnetworks of either vimentin or cytokeratin type.
 ...
PMID:Specific types of prosomes are associated to subnetworks of the intermediate filaments in PtK1 cells. 128 72

Exogenous adenosine diphosphate (ADP), the most potent mitogen for nontransformed African green monkey kidney epithelial cells of the BSC-1 line, rapidly alters the appearance of the cell monolayer. Examination of the cells with indirect immunofluorescence using monoclonal antibodies reveals a considerable reorganization of cytokeratin filaments without a major change in the pattern of microtubules or microfilaments. In untreated confluent cells, cytokeratin filaments are predominantly confined to a star-like spot in the perinuclear area, but these can be seen to begin to spread within 2 min after addition of ADP. The effect is particularly notable using anti-cytokeratin 8 antibodies. At 6 h this process is complete and produces a well-developed filamentous network throughout the cell. By 12 h, the network appears to collapse, so that the filaments again form a spot in the perinuclear area, a process that is complete by 24 h. Immunoblotting of total cellular proteins reveals no apparent alterations in the amounts of several species of cytokeratins, including cytokeratin 8 and 18, at 3 or 24 h after exposure to ADP. Other purine and pyrimidine nucleotides which do not stimulate DNA synthesis in these cells fail to alter cytokeratin organization, and there is no apparent alteration in the distribution of vimentin, another intermediate filament protein. The rapid ADP-induced cytokeratin reorganization appears to coincide with the induction of early growth-response gene transcription in these cells and may be correlated with the capacity of ADP to subsequently initiate DNA synthesis. This dramatic and reversible cytokeratin reorganization immediately after exposure to ADP may be an important step in the mitogenic signal transduction pathway.
 ...
PMID:Cytokeratin reorganization induced by adenosine diphosphate in kidney epithelial cells. 137 34

The influence of the antitumor drug cis-diamminedichloroplatinum(II) ('cisplatin') upon the structural pattern of the main cytoskeletal components, i.e. microtubules, intermediate filaments and microfilaments, was investigated in squamous carcinoma cells derived from the mouse stomach (G 22) or the human lung (L 266) and growing in vitro as monolayer cultures. The studies were performed by the indirect immunofluorescence technique using monoclonal antibodies against alpha-tubulin, type 19 cytokeratin and actin at the end of a 90-min exposure to 2.5 x 10(-6), 5 x 10(-6) or 10(-5) mol cisplatin/l and a subsequent 24-h recovery period. Under the influence of cisplatin, the cytoskeletal tubules and filaments, which were distributed in untreated cells as a finely organized network spreading through the whole cytoplasm like a spider's web, collapsed and aggregated to dense and circularly arranged bands of bright immunofluorescence around the nucleus or to cap-like structures apposing the nucleus. These phenomena developed in clear dependence upon the dose of cisplatin applied and were observable in a modified manner and to a different degree with the three structural elements of the cytoskeleton. During the subsequent 24-h interval, during which the cells were allowed to recover in drug-free growth medium, the before-mentioned collapse of the cytoskeletal network was only partially reversible following previous treatment with the medium (5 x 10(-6) mol/l) and the high (10(-5) mol/l) dose of cisplatin and restored totally to the normal structural pattern of untreated control cells when the low dose of 2.5 x 10(-6) mol cisplatin/l had been administered before. These results give evidence that the DNA cannot be the only cellular target for the antitumor drug cisplatin, but that it also effects other intracellular lesions which cause structural alterations of cellular organelles independently of the primary molecular attack at nuclear DNA strands. Probably, these additional interactions fortify the antiproliferative effect and contribute to the achievement of important biological and cytological effects of cisplatin such as growth inhibition or giant cell formation.
 ...
PMID:Changes in the cytoskeleton pattern of tumor cells by cisplatin in vitro. 160 25

The role of cytokeratin filaments in the function of hepatocytes was investigated using a nickel-treated hepatocyte in vitro model. Cytokeratin intermediate filaments were selectively dissociated from the cell cortex by nickel treatment. Cytokeratins and ubiquitin were observed using immunofluorescence and immunoelectron microscopy. Hepatocytic function was assessed by visualizing uptake, transhepatic transport and secretion of fluorescein diacetate and horseradish peroxidase into the bile canaliculi. In control primary cultures, most of the bile canaliculi were surrounded by an inner layer of actin filaments and an outer pericanalicular sheath of cytokeratin filaments and microtubules. The cytoplasmic distribution of ubiquitin was diffuse and particulate. After treatment with NiCl2 (150 micrograms/ml) for 24 hr, the cytokeratin filaments and desmoplakin became focally detached from the cell cortex and retracted to form an aggregate around the nucleus. These aggregates were associated with intense ubiquitin immunoreactivity. Only a few attachments of the cytokeratin filaments to the cell cortex remained. F-actin remained attached to the cell cortex in the areas where the cytokeratin filaments had become detached. The pericanalicular sheath of cytokeratin filaments and the bile canaliculi disappeared and actin was dispersed over the entire cell periphery. Fluorescein diacetate secretion and horseradish peroxidase uptake were almost completely absent in the hepatocytes treated with nickel. The effects of nickel persisted 24 hr after its removal from the medium. It is concluded that cytokeratin intermediate filaments play a critical role in the formation of the bile canaliculus, secretion of fluorescein diacetate and uptake of horseradish peroxidase. Further, our study indicates that cytokeratin ubiquitination occurs during collapse and aggregation of the cytokeratin filaments. The formation of cytokeratin-ubiquitin conjugates during aggregation suggests a role of ubiquitin in the control of cytokeratin organization in hepatocytes in the response to cell stress.
 ...
PMID:Role of cytokeratin intermediate filaments in transhepatic transport and canalicular secretion. 169 Jan 70

The cytoplasm of eukaryotic cells contain a series of three filamentous structures, microtubules, microfilaments, and intermediate filaments that are termed the cytoskeleton. Cytokeratin, one type of intermediate filament, has no known physiological function, yet, can comprise up to 30% of the total cytoplasmic protein content. As there are no selective toxins to cytokeratins, it is not known if alterations to these hydrophobic filaments is a lethal event. Cyclosporine A, a novel hydrophobic immunosuppressant compound used to prevent allograft rejection, may show a selective toxicity to the cytokeratin filaments. This effect is seen in PtK2 cell cultures as a single large perinuclear aggregate of collapsed cytokeratin filaments (5 mM, 72 hr). Microtubules and microfilaments are not affected in PtK2 cell cultures (5 mM, 72 hr). Increased LDH levels into cell culturing media occur soon after cyclosporine exposure to PtK2 cell cultures (5 mM, 2 hr). Cytokeratin filaments show no changes at 12 hr exposure but show thickening, decreased plasma membrane attachments and some peri-nuclear ring formations at 24 hr (5 mM, 24 hr). Cyclosporine G, an analog of cyclosporine A, does not exhibit the cytokeratin filament collapse (5 mM, 72 hr). The effect of cyclosporine A on DNA binding protein (Mr 64 kd), believed to be a nuclear scaffolding protein related to intermediate filaments, exhibited an early invagination and folding of the nuclear membrane (5 mM, 4 hr). Due to a hydrophobic bonding potential between cyclosporine A and cytokeratin and cytokeratin-like intermediate filaments, cyclosporin A may be a selective cytokeratin toxin. Alteration of the cytokeratin filaments in PtK2 cell cultures may be a lethal event.
 ...
PMID:Selective alteration of cytokeratin intermediate filament by cyclosporine A is a lethal toxicity in PTK2 cell cultures. 171 36

The human papillomaviruses (HPV) are associated specifically with epithelial lesions, ranging from benign warts to invasive carcinoma. The virus encodes three late proteins, which are produced only in terminally differentiating keratinocytes, two of which are structural components of the virion. The third, E1-E4, is derived primarily from the E4 open reading frame, which represents a region of maximal divergence between different HPV types. E1-E4 does not seem to be a component of the virus particle or to be needed for transformation in vitro, but accumulates in the cytoplasm, where in certain benign lesions it can comprise 20-30% of total cell protein. We show here that expression of the HPV-16 E1-E4 protein in human keratinocytes (the natural host cell for HPV infection) results in the total collapse of the cytokeratin matrix. Tubulin and actin networks are unaffected by E1-E4, as are the nuclear lamins.
 ...
PMID:Specific interaction between HPV-16 E1-E4 and cytokeratins results in collapse of the epithelial cell intermediate filament network. 171 19

Recent studies indicate that the cytoskeleton may be involved in modulating tissue-specific gene expression in mammalian cells. We have studied the role of the cytoskeleton in regulating milk protein synthesis and secretion by primary mouse mammary epithelial cells cultured on a reconstituted basement membrane that promotes differentiation. After 8 days in culture, cells were treated with cytochalasin D (CD) (0.5-1 micrograms/ml) to alter actin filaments or acrylamide (Ac) (5 mM) to alter intermediate filaments (cytokeratins). CD inhibited synthesis of most proteins in a concentration-dependent manner, with beta-casein being the first affected. In contrast, Ac increased protein synthesis and secretion by 17-31% after a 12 hr treatment. Polyacrylamide gel electrophoresis of total secreted proteins indicates that synthetic rates of most proteins were increased equally by Ac treatment. This increase is apparently controlled at the level of translation, because control and Ac-treated cells contained the same amount of poly-A+ RNA, and neither CD nor Ac altered mRNA levels for beta-casein. There was also no indication that either CD or Ac can induce the expression of milk proteins in quiescent cells cultured on a plastic substratum. In conjunction with the biochemical studies, changes in cytoskeletal morphology caused by the drug treatments were analyzed by immunofluorescence microscopy. As has been observed in other cell types, low concentrations of CD caused cells to round up by disrupting actin filaments. Ac treatment slightly decreased the intensity of actin staining, but no changes in microfilament organization were observed. Ac-treated cells showed slight disorganization of the cytokeratin filaments, with some peripheral interfibrillar bundling, but the cytokeratin network did not collapse and no retraction of cell extensions or breakdown of cell-cell contacts was observed. These results confirm previous reports that the actin cytoskeleton may play a role in regulating tissue-specific protein synthesis. How Ac stimulates protein synthesis is unknown, but it is unlikely that this effect is directly mediated through intermediate filaments.
 ...
PMID:Modulation of milk protein synthesis through alteration of the cytoskeleton in mouse mammary epithelial cells cultured on a reconstituted basement membrane. 199 14

Expression of intermediate filament (IF) isotypes was studied in six human and two murine melanoma cell lines. With one exception, these lines expressed IFs only of the vimentin type; neurofilament peptides, desmin and GFAP were not detected. However, the M5 human melanoma line also expressed extensive cytokeratin tonofilament arrays, as visualized by immunofluorescence with a panel of eleven monoclonal antibodies and hetero-antisera to cytokeratins; only the keratin 19-specific antibody BA16 did not react. By 2 D gel electrophoresis, five major keratin peptides were detected (keratins 7, 8, 13, 17 and 18), and an additional 57 kD peptide was detected on immunoblots with several antikeratin antibodies. Also observed in M5 cells was focal collapse of tonofilament arrays in mitotic cells. All the melanoma lines tested were positive for S100; M5 and two other cell lines were also positive for the 220-240 kD neuroectoderm-associated cell-surface differentiation antigen defined by monoclonal antibody UJ 127:11. In all the melanoma cell lines, secretion of extracellular matrix proteins (fibronectin, laminin and collagen type IV) was sparse or absent, and all were negative for the epithelial cell markers HMG-1 and HMG-2. Co-expression of keratin and vimentin by a melanoma cell line is discussed in the light of recent controversy concerning expression of cytokeratins by other neoplasms of putative neuroectodermal origins.
 ...
PMID:Phenotypic analysis of cultured melanoma cells. Expression of cytokeratin-type intermediate filaments by the M5 human melanoma cell line. 242 48

In order to investigate the relationship of different cytokeratins within one cell, monoclonal antibodies directed against three trophectoderm cytokeratins TROMA 1, 2 and 3 were microinjected into mouse teratocarcinoma-derived trophoblastoma cells and indirect immunofluorescence tests were used to follow the subsequent localization of their respective antigens Endo A, B and C. Microinjection of TROMA 1 or 2 resulted in the perinuclear collapse of Endo A, B and C-containing filaments. Microinjection of TROMA 3 resulted in the perinuclear collapse of filaments containing Endo A and B, whereas Endo C condensed into cytoplasmic aggregates which appear as speckles in the fluorescence microscope. The speckles were electron microscopically located using indirect gold-labeling techniques and had a dense, granulous structure. They were often found to be associated with microtubules, although colchicine treatment before microinjection did not interfere with speckle formation. These experiments demonstrate that cytokeratins can become differentially distributed within the cytoplasm after microinjection of an anti-cytokeratin monoclonal antibody. Since Endo A is a type II cytokeratin and Endo B and C are type I cytokeratins, these results suggest that different members of one cytokeratin subfamily may be associated with cytokeratin filaments which have different functions within the same cell.
 ...
PMID:Differential distribution of cytokeratins after microinjection of anti-cytokeratin monoclonal antibodies. 244 90

Several neurotoxic compounds cause aggregation of neurofilaments in peripheral axons. This may represent a primary action of these chemicals or a secondary response to other cellular damage. To distinguish between these possibilities, the effects of acrylamide and 2,5-hexanedione (2,5-HD) on vimentin were examined in PtK2 cultured cells. Vimentin intermediate filaments were chosen because they are closely related, in structure, to neurofilaments. Effects on other components of the cytoskeleton (cytokeratin filaments, microtubules, and microfilaments) were also determined. Both acrylamide and 2,5-HD caused aggregation of vimentin filaments in a concentration-dependent fashion; these effects occurred at a lower concentration than alterations in other cytoskeletal filaments. The effects of both acrylamide and 2,5-HD were reversible, except at high concentrations of 2,5-HD. Crosslinking of cytoskeletal proteins was also examined. High-molecular-weight proteins with vimentin-like immunoreactivity were detected on blots from cells exposed to high concentrations of 2,5-HD. No crosslinked protein was detected after acrylamide treatment. These results suggest that both acrylamide and 2,5-HD cause a primary collapse of vimentin intermediate filaments in cultured cells. The initial redistribution of vimentin filaments occurred without apparent crosslinking of cytoskeletal proteins. The aggregation of vimentin filaments in cultured cells and of neurofilaments in vivo may share a common molecular mechanism.
 ...
PMID:Cytoskeletal effects of acrylamide and 2,5-hexanedione: selective aggregation of vimentin filaments. 246 60


1 2 3 4 Next >>