Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Keywords: EXPRESSION ; GROWTH ; IN-VITRO ; INHIBITOR ; proliferation ; CELL ; CELL-PROLIFERATION ; Germany ; human ; IN-VIVO ; VITRO ; VIVO ; microarray ; PROTEIN ; PROTEINS ; RNA ; DRUG ; SURGERY ; PATIENT ; REDUCTION ; TRANSPLANTATION ; RAT ; CONTRAST ; mechanisms ; SKIN ; fibroblasts ; ACID ; PCR ; NUCLEOTIDES ; EXTRACELLULAR-MATRIX ; ADHESION ; MIGRATION ; cytoskeleton ; POLYMERASE-CHAIN-REACTION ; SMOOTH-MUSCLE ; COMPLICATIONS ; BIOPSY ; CHAIN ; fibroblast ; DEHYDROGENASE ; RECIPIENTS ; HUMAN FIBROBLASTS ; cell adhesion ; mycophenolic acid ; TECHNOLOGY ; B-LYMPHOCYTES ; ENGLAND ; ACTIN ; DYSFUNCTION ; synthesis ; NUCLEOTIDE ; CYCLOSPORINE ; MOFETIL ; KIDNEY-TRANSPLANT
    Abstract: Mycophenolic acid (MPA) is a potent inhibitor of the inosine monophosphate dehydrogenase and used as an immunosuppressive drug in transplantation. MPA inhibits proliferation of T- and B-lymphocytes by guanosine depletion. Since fibroblasts rely on the de novo synthesis of guanosine nucleotides, it is assumed that MPA interacts with fibroblasts causing an increased frequency of wound healing problems. We show a downregulation of the cytoskeletal proteins vinculin, actin and tubulin in fibroblasts exposed to pharmacological doses of MPA using microarray technology, real-time polymerase chain reaction (PCR) and Western blot. This reduction in RNA and protein content is accompanied by a substantial rearrangement of the cytoskeleton in MPA-treated fibroblasts as documented by immunofluorescence. The dysfunctional fibroblast growth was validated by scratch test documenting impaired migrational capacity. In contrast, cell adhesion was increased in MPA-treated fibroblasts. The results of the cultured human fibroblasts were applied to skin biopsies of renal transplant recipients. Skin biopsies of patients treated with MPA expressed less vinculin, actin and tubulin as compared to control biopsies that could explain potential wound healing problems posttransplantation. The perspective of MPA-induced cytoskeletal dysfunction may go beyond wound healing disturbances and may have beneficial effects on (renal) allografts with respect to scarring
    Type of Publication: Journal article published
    PubMed ID: 18786225
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Keywords: CELLS ; EXPRESSION ; INHIBITOR ; Germany ; IN-VIVO ; VIVO ; GENE ; GENE-EXPRESSION ; PROTEIN ; MOLECULES ; ACTIVATION ; MECHANISM ; DOMAIN ; CONTRAST ; mechanisms ; TRANSACTIVATOR ; MOLECULE ; virus ; ELEMENT ; RESPONSE ELEMENT ; gene expression ; ASSAY ; PROMOTER ; Western-blot ; ELEMENTS ; PROMOTERS ; acetylation ; DNA-BINDING ; REGION ; REGIONS ; transactivation ; TRANS-ACTIVATION ; HISTONE ACETYLTRANSFERASE ; western blot ; foamy virus ; REGULATOR ; REGULATORS ; COACTIVATORS P300 ; INTERNAL PROMOTER ; ACETYLTRANSFERASE ; C-TERMINAL DOMAIN ; CBP ; CBP/P300 ; HISTONE ACETYLTRANSFERASES ; NUCLEAR FACTOR-I
    Abstract: Background: Foamy virus Bel1/Tas trans-activators act as key regulators of gene expression and directly bind to Bel1 response elements (BRE) in both the internal and the 5' LTR promoters leading to strong transcriptional trans-activation. Cellular coactivators interacting with Bel1/Tas are unknown to date. Results: Transient expression assays, co-immunoprecipitation experiments, pull-down assays, and Western blot analysis were used to demonstrate that the coactivator p300 and histone acetyltransferase PCAF specifically interact with the retroviral trans-activator Bel1/Tas in vivo. Here we show that the Bel1/Tas-mediated trans-activation was enhanced by the coactivator p300, histone acetyltransferases PCAF and SRC-1 based on the crucial internal promoter BRE. The Bel1/Tas-interacting region was mapped to the C/H1 domain of p300 by co-immunoprecipitation and pull-down assays. In contrast, coactivator SRC-1 previously reported to bind to the C-terminal domain of p300 did not directly interact with the Bel1 protein but nevertheless enhanced Bel1/Tas-mediated trans-activation. Cotransfection of Bel1/Tas and p300C with an expression plasmid containing the C/H1 domain partially inhibited the p300C-driven trans-activation. Conclusions: Our data identify p300 and PCAF as functional partner molecules that directly interact with Bel1/Tas. Since the acetylation activities of the three coactivators reside in or bind to the C-terminal regions of p300, a C/H1 expression plasmid was used as inhibitor. This is the first report of a C/H1 domain-interacting retroviral trans-activator capable of partially blocking the strong Bel1/Tas-mediated activation of the C-terminal region of coactivator p300. The potential mechanisms and functional roles of the three histone and factor acetyltransferases p300, PCAF, and SRC-1 in Bel1/Tas-mediated trans-activation are discussed
    Type of Publication: Journal article published
    PubMed ID: 15350211
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    Keywords: SURGERY ; TRANSPLANTATION ; VIVO ; VITRO ; IN-VIVO ; human ; IN-VITRO ; proliferation ; fibroblast ; MIGRATION ; ADHESION ; ACID ; ENGLAND ; mycophenolic acid
    Type of Publication: Meeting abstract published
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...