Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Deletion and mutagenesis of the 5'-flanking region of the human transcobalamin II (TC II) transfected in human intestinal epithelial Caco-2 cells have revealed that TC II promoter activity is: (a) very weak; (b) restricted to a core region (-29 to -163) that contained multiple transcription initiation sites; (c) not dependent on other potential elements, such as a distally localized CCAAT box, a CF1, a HIP1 binding motif and a MED-1 element; (d) modulated weakly by a positive-acting GC box (-568-GAGGCGGTGC) and strongly by a proximal GC/GT overlapping box (-179 CCCCCGCCCCACCCC). Gel shift and immunosupershift analyses demonstrated that both the positive-acting GC box and the negative-acting GC/GT box were recognized by Sp1 and Sp3. Co-transfection studies using Sp1 and/or Sp3 expression plasmids revealed that while Sp1 stimulated, Sp3 repressed Sp1-mediated transactivation of TC II transcription. The proximal GC/GT box also acted as a negative element in human chronic myelogenous leukemia K-562 and HeLa cells. These results suggest that tissue/cell specific expression of the TC II gene may be controlled by the relative ratios of Sp1 and Sp3 that bind to the GC/GT box and the weak promoter activity of TC II is due to the transcriptional repression caused by the binding of Sp3 to the proximal GC/GT box.
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PMID:Characterization of the human transcobalamin II promoter. A proximal GC/GT box is a dominant negative element. 963 63

In vitro degradation and chondrocyte-encapsulation of chitosan hydrogel made of crosslinkable and water-soluble chitosan derivative (CML) at neutral pH and body temperature were studied with respect to weight loss, cytoviability, DNA content and cell morphology. In vitro degradation of the chitosan hydrogels was sensitive to their crosslinking degree and existence of lysozyme in the solution. Chitosan hydrogel (Gel-I5) fabricated from 1% CML and 5mM ammonium persulfate (APS)/N,N,N',N'-tetramethylethylenediamine (TMEDA) displayed no degradation in phosphate buffered saline (PBS) after 18d, but degraded completely at 8d in 1mg/ml lysozyme/PBS. The chitosan hydrogel fabricated from 10mM APS/TMEDA was non-degradable even in lysozyme/PBS solution after 18d. The hydrogel loaded with chondrocytes in cell culture medium, however, was susceptible to degradation during the in vitro culture. In vitro culture of the encapsulated chondrocytes in the chitosan hydrogel demonstrated that the cells retained round shaped morphology and could survive through a 12d-culture period, although the DNA assay detected an overall reduction of the cell number. These features provide a great opportunity to use the chitosan hydrogel as an injectable scaffold in tissue engineering and orthopaedics.
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PMID:Covalently crosslinked chitosan hydrogel: properties of in vitro degradation and chondrocyte encapsulation. 1695

Pick's disease is a subset of fronto-temporal dementia characterised by severe atrophy of the temporal and frontal lobes due to marked neuronal loss accompanied by astrocytic gliosis enriched in glial acidic protein. The remaining neurones have intracytoplasmic inclusions composed of hyperphosphorylated tau, called Pick bodies, in addition to hyperphosphorylated tau in astrocytes and oligodendrocytes. Gel electrophoresis and western blotting using markers of glycoxidation (advanced glycation end products, N-carboxyethyl-lysine and N-carboxymethyl-lysine: AGE, CEL, CML, respectively) and lipoxidation (4-hydroxy-2-nonenal: HNE, and malondialdehyde-lysine: MDAL) were used in the frontal and occipital cortex in three Pick's disease cases and three age-matched controls. In Pick's disease, increased AGE, CML, CEL, HNE and MDAL bands of about 50 kDa were observed in the frontal cortex (but not in the occipital cortex) in association with increased density of glial acidic protein bands. Bi-dimensional gel electrophoresis and western blotting also disclosed increased amounts and numbers of glial acidic protein isoforms in the frontal cortex in Pick's disease. Moreover, redox proteomics showed glycoxidation, as revealed with anti-CEL antibodies and lipoxidation using anti-HNE antibodies, of at least three glial acidic protein isoforms. The present results demonstrate that glial acidic protein is a target of oxidative damage in the frontal cortex in Pick's disease.
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PMID:Glial fibrillary acidic protein is a major target of glycoxidative and lipoxidative damage in Pick's disease. 1698 45

Signaling initiated by the BCR-ABL1 kinase causes chronic myelogenous leukemia (CML). Recently, we reported that expression of Fyn, a Src kinase, is heightened in CML cells and patient specimens and confers in vitro and in vivo proliferative advantages. Fyn is regulated by redox, and because BCR-ABL1 raises intracellular oxidant levels, which have been implicated in CML progression, we explored the molecular regulation of Fyn. Here we identify the transcription factors that drive redox- and BCR-ABL1-dependent Fyn expression. Promoter deletion analysis in 293T, BaF3, BaF3-p210, and K562 cells identified the region essential for basal transcriptional activity. Mutation of Sp1 and Egr1 binding sites within the essential region diminished Fyn promoter activity and identified Egr1 as conferring redox sensitivity. Gel shift and chromatin immunoprecipitation assays confirmed the binding of Sp1 and Egr1 to the promoter fragments. Importantly, knockdown of Sp1 or Egr1 with small interference RNA or inhibition of Sp1 binding by mithramycin A repressed Fyn protein expression. Our work is the first to define transcription factors that are responsible for endogenous, oxidative stress-dependent and BCR-ABL1-dependent Fyn expression.
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PMID:Oxidative stress promotes transcriptional up-regulation of Fyn in BCR-ABL1-expressing cells. 1913 39


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