Your email was sent successfully. Check your inbox.

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

Proceed reservation?

Export
  • 1
    Keywords: RECEPTOR ; APOPTOSIS ; CELLS ; EXPRESSION ; CELL ; Germany ; human ; DEATH ; CLONING ; GENE-EXPRESSION ; PROTEIN ; SAMPLE ; SAMPLES ; DIFFERENTIATION ; LIGAND ; MECHANISM ; CONTRAST ; mechanisms ; IN-SITU ; NEOPLASIA ; CELL-DEATH ; DECREASE ; RECEPTORS ; SMALL-INTESTINE ; TRAIL ; protein expression ; LACKING ; molecular ; RECOMBINANT ; MOLECULAR-MECHANISM ; VARIANT ; INCREASE ; CELL-SURFACE EXPRESSION ; PH ; regulation ; development ; MOLECULAR-MECHANISMS ; methods ; cell death ; CELIAC-DISEASE ; death receptor ; USA ; LIGAND TRAIL ; HOMEOSTASIS ; INCREASES ; apoptotic ; MUCOSAL ; ACYL-COA-SYNTHETASE-5 ; HUMAN SMALL-INTESTINE ; IMPAIRED EXPRESSION
    Abstract: Background & Aims: The constant renewal of enterocytes along the crypt-villus axis (CVA) of human small intestine is due to cell-inherent changes resulting in the apoptotic cell death of senescent enterocytes. The aim of the present study was to examine underlying molecular mechanisms of the cell death at the villus tip. Methods: Characterization of human acyl-coenzyme A (CoA) synthetase 5 (ACSL5) was performed by cloning, recombinant protein expression, biochemical approaches, and several functional and in situ analyses. Results: Our data show that different amounts of acyl-CoA synthetase 5-full length (ACSL5-fl) and a so far unknown splice variant lacking exon 20 (ACSL5-Delta 20) are found in human enterocytes. In contrast with the splice variant ACSL5-Delta 20, recombinant and purified ACSL5-fl protein is active at a highly alkaline pH. Over expression of ACSL5-fl protein is associated with a decrease of the anti-apoptotic FLIP protein in a ceramide-dependent manner and an increased cell-surface expression of the death receptor TRAIL-RI. Expression analyses revealed that the ACSL5-fl/ACSL5-Delta 20 ratio increases along the CVA, thereby sensitizing ACSL5-fl-dominated cells at the villus tip to the death ligand TRAIL, which is corroborated by functional studies with human small intestinal mucosal samples and an immortalized human small intestinal cell fine. Conclusions: Our results suggest an ACSL5-dependent regulatory mechanism that contributes to the cellular renewal along the CVA in human small intestine. Deregulation of the ACSL5-fl/ACSL5-Delta 20 homeostasis in the maturation and shedding of cells along the CVA might also be of relevance for the development of intestinal neoplasia
    Type of Publication: Journal article published
    PubMed ID: 17681178
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Keywords: CELLS ; EXPRESSION ; CELL ; Germany ; MODEL ; DISEASE ; GENE ; GENE-EXPRESSION ; PROTEIN ; PROTEINS ; DIFFERENTIATION ; MONOCLONAL-ANTIBODY ; MATURATION ; antibodies ; antibody ; MOUSE ; IN-SITU ; immunohistochemistry ; gene expression ; CELL-LINE ; LINE ; SURFACE ; MONOCLONAL-ANTIBODIES ; STRATEGIES ; CELIAC-DISEASE ; EXPRESSION PROFILES ; GLUTEN ; STRATEGY ; DNAJ ; J-DOMAIN
    Abstract: Background: Maturation of enterocytes along the small intestinal crypt-villus axis is associated with significant changes in gene expression profiles. fls485 coding a putative chaperone protein has been recently suggested as a gene involved in this process. The aim of the present study was to analyze fls485 expression in human small intestinal mucosa. Methods: fls485 expression in purified normal or intestinal mucosa affected with celiac disease was investigated with a molecular approach including qRT-PCR, Western blotting, and expression strategies. Molecular data were corroborated with several in situ techniques and usage of newly synthesized mouse monoclonal antibodies. Results: fls485 mRNA expression was preferentially found in enterocytes and chromaffine cells of human intestinal mucosa as well as in several cell lines including Rko, Lovo, and CaCo2 cells. Western blot analysis with our new anti-fls485 antibodies revealed at least two fls485 proteins. In a functional CaCo2 model, an increase in fls485 expression was paralleled by cellular maturation stage. Immunohistochemistry demonstrated fls485 as a cytosolic protein with a slightly increasing expression gradient along the crypt-villus axis which was impaired in celiac disease Marsh IIIa-c. Conclusions: Expression and synthesis of fls485 are found in surface lining epithelia of normal human intestinal mucosa and deriving epithelial cell lines. An interdependence of enterocyte differentiation along the crypt-villus axis and fls485 chaperone activity might be possible
    Type of Publication: Journal article published
    PubMed ID: 20205943
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...